DNA molecule, structural features and functions. The structure of DNA: features, scheme

The first evidence of the role of DNA as a carrier of the hereditary information of organisms attracted great attention to the study of nucleic acids. In 1869, F. Miescher isolated a special substance from the nuclei of cells, which he called nuclein. After 20 years, this name was replaced by the term nucleic acid. In 1924, R. Felgen developed a method for the cytological recognition of nucleic acids through their specific staining and showed that DNA is localized in the nuclei of cells, and RNA in the cytoplasm. In 1936 A.N. Belozersky and I.I. Dubrovskaya isolated pure DNA from the nuclei of plant cells. By the beginning of the 1930s. the basic chemical principles of the structure of nucleic acid sugars were elucidated, and in 1953 a structural model of DNA was created.

The main structural unit of nucleic acids is nucleotide, which consists of three chemically different parts connected by covalent bonds (Fig. 5.2).

Rice. 5.2. Structural formulas: a- nucleotides; b- DNA; v - RNA (see also p. 110)

Rice. 5.2. Ending. Structural formulas: a- nucleotides; 6 - DNA; v- RNA

The first part is a sugar containing five carbon atoms: deoxyribose in DNA and ribose in RNA.

The second part of the nucleotide - a purine or pyrimidine nitrogenous base, covalently attached to the first carbon atom of the sugar, forms a structure called nucleoside. DNA contains purine bases - adenine(A) and guanine(D) - and pyrimidine bases - thymine(T) and cytosine(C). The corresponding nucleosides are called deoxyadenosine, deoxyguanosine, deoxythymidine and deoxycytidine. RNA contains the same purine bases as DNA, the pyrimidine base cytosine, and instead of thymine it contains uracil(U); the corresponding nucleosides are called adenosine, guanosine, uridine and cytidine.

The third part of the nucleotide is a phosphate group, which connects neighboring nucleosides into a polymer chain through phosphodiester bonds between the 5-carbon atom of one sugar and the 3 "carbon atom of another (Fig. 5.2, b, v). Nucleotides are called nucleosides with one or more phosphate groups attached by ester bonds to the 3 "- or 5-carbon atoms of the sugar. Nucleotide synthesis precedes the synthesis of nucleic acids, respectively, nucleotides are products of chemical or enzymatic hydrolysis of nucleic acids.

Nucleic acids are very long polymeric chains consisting of mononucleotides connected by 5- and 3'-phosphodiester bonds. An intact DNA molecule contains, depending on the type of organism, from several thousand to many millions of nucleotides, an intact RNA molecule - from 100 to 100 thousand or more nucleotides.

The results of analyzes of the nucleotide composition of DNA of various species by E. Chargaff showed that the molecular ratio of various nitrogenous bases - adenine, guanine, thymine, cytosine - varies widely. Consequently, it was proved that DNA is not at all a monotonous polymer consisting of identical tetranucleotides, as was assumed in the 1940s. XX centuries, and that it fully possesses the complexity necessary for the preservation and transmission of hereditary information in the form of a specific sequence of nucleotide bases.

Research by E. Chargaff also revealed a feature inherent in all DNA molecules: the molar content of adenine is equal to the content of thymine, and the molar content of guanine is equal to the content of cytosine. These equalities are called the Chargaff equivalence rule: [A] = [T], [G] = [C]; the number of purines is equal to the number of pyrimidines. Depending on the species, only the ratio ([A] + [T]) / ([G] + [C]) changes (Table 5.1).

	The composition of the bases				Attitude		Asymmetry
					grounds
							(A + T)/(G + C)
Animals
Turtle
sea ​​crab
Sea urchin
Plants, mushrooms
wheat germ
Mushroom Aspergillus niger
bacteria
Escherichia coli
Staphylococcus aureus
Clostridium perfringens
Brucela abortus
Sarcina lutea
bacteriophages
FH 174 (viral form)
FH 174 (replicative form)

The base ratio is called nucleotide(specific) specificity. In Chargaff's discovery, an important structural feature of DNA was formulated, which was later reflected in the structural model of DNA by J. Watson and F. Crick (1953), which actually showed that Chargaff's rules do not impose any restrictions on the possible number of combinations of different base sequences that can form molecules DNA.

The position on nucleotide specificity formed the basis of a new branch of biology - gene systematics, which operates by comparing the composition and structure of nucleic acids to build a natural system of organisms.

According to the Watson-Crick model, a DNA molecule consists of two polynucleotide chains (strands, strands) connected to each other by transverse hydrogen bonds between nitrogenous bases according to the complementary principle (adenine of one chain is connected by two hydrogen bonds to thymine of the opposite chain, and guanine and cytosine of different chains are connected to each other by three hydrogen bonds). In this case, two Polynucleotide chains of one molecule are antiparallel, i.e. opposite the 3 "end of one chain is the 5" end of the other chain and vice versa (Fig. 5.3). However, it should be borne in mind the current data that the genetic material of some viruses is represented by single-stranded (single-stranded) DNA molecules. Based on the data of X-ray diffraction analysis of DNA, J. Watson and F. Crick also concluded that its double-stranded molecule has a secondary structure in the form of a spiral, twisted in the direction from left to right, which later became known as the 5-form (Fig. 5.4). To date, it has been proven that, in addition to the most common 5-form, it is possible to detect DNA segments that have a different configuration - as right-handed (forms A, C), and twisted from right to left (left-handed, or Z-shape) (Fig. 5.4). There are certain differences between these forms of the secondary structure of DNA (Table 5.2). So, for example, the distance between two adjacent pairs of nitrogenous bases in a double-stranded helix, expressed in nanometers (nm), for the 5-form and Z-form is characterized by different values ​​(0.34 and 0.38 nm, respectively). On fig. 5.5 shows modern three-dimensional models of "left-handed" and "right-handed" forms of DNA.

Rice. 5.3. schematic representation of the primary structure of a fragment of a double-stranded DNA molecule: A - adenine; G - guanine; T - thymine; C - cytosine

Rice. 5.4.

Table 5.2

Properties of different shapes of DNA double helixes

RNA molecules, depending on their structural and functional features, are divided into several types: informational (matrix) RNA (mRNA, or mRNA), ribosomal RNA (rRNA), transfer RNA (tRNA), small nuclear RNA (snRNA), etc. Unlike from DNA, RNA molecules are always single-stranded (single-stranded). However, they can form more complex (secondary) configurations due to the complementary connection of individual sections of such a chain based on the interaction of complementary nitrogenous bases (A-U and G-C). As an example, consider the clover-leaf configuration for the phenylalanine transfer RNA molecule (Fig. 5.6).

Rice. 5.6.

In 1953, D. Watson and F. Crick proposed a model of the DNA structure, which was based on the following postulates:

• 1. DNA is a polymer consisting of nucleotides connected by 3"- and 5"-phosphodiester bonds.
• 2. The composition of DNA nucleotides obeys Chargaff's rules.
• 3. The DNA molecule has a double helix structure resembling a spiral staircase, as evidenced by X-ray patterns of DNA strands, first obtained by M. Wilkins and R. Franklin.
• 4. The structure of the polymer, as shown by acid-base titration of native (natural) DNA, is stabilized by hydrogen bonds. Titration and heating of native DNA causes a noticeable change in its physical properties, in particular viscosity, converting it into a denatured form, and covalent bonds are not destroyed.

Content

The abbreviation cellular DNA is familiar to many from the school biology course, but few can easily answer what it is. Only a vague idea of ​​heredity and genetics remains in the memory immediately after graduation. Knowing what DNA is, what impact it has on our lives, can sometimes be very necessary.

DNA molecule

Biochemists distinguish three types of macromolecules: DNA, RNA, and proteins. Deoxyribonucleic acid is a biopolymer that is responsible for transmitting data on hereditary traits, characteristics and development of a species from generation to generation. Its monomer is a nucleotide. What are DNA molecules? It is the main component of chromosomes and contains the genetic code.

DNA structure

Previously, scientists imagined that the DNA structure model is periodic, where the same groups of nucleotides (combinations of phosphate and sugar molecules) are repeated. A certain combination of nucleotide sequence provides the ability to "encode" information. Thanks to research, it turned out that the structure of different organisms is different.

American scientists Alexander Rich, David Davis and Gary Felsenfeld are especially famous in studying the question of what DNA is. In 1957, they presented a description of a three-helix nucleic acid. After 28 years, the scientist Maxim Davidovich Frank-Kamenitsky demonstrated how deoxyribonucleic acid, which consists of two helices, is folded into an H-shaped form of 3 strands.

The structure of deoxyribonucleic acid is double-stranded. In it, nucleotides are connected in pairs to form long polynucleotide chains. These chains, by means of hydrogen bonds, make possible the formation of a double helix. The exception is viruses that have a single-stranded genome. There are linear DNA (some viruses, bacteria) and circular (mitochondria, chloroplasts).

Composition of DNA

Without knowing what DNA is made of, there would be no achievement in medicine. Each nucleotide consists of three parts: a pentose sugar residue, a nitrogenous base, and a phosphoric acid residue. Based on the characteristics of the compound, acids can be called deoxyribonucleic or ribonucleic. DNA contains a huge number of mononucleotides from two bases: cytosine and thymine. In addition, it contains pyrimidine derivatives, adenine and guanine.

There is a definition of DNA in biology - junk DNA. Its function is still unknown. An alternative version of the name is "non-coding", which is not true, because it contains coding proteins, transposons, but their purpose is also a mystery. One of the working hypotheses suggests that a certain amount of this macromolecule contributes to the structural stabilization of the genome in relation to mutations.

Where is

The location within the cell depends on the characteristics of the species. In unicellular DNA is located in the membrane. In other living beings, it is located in the nucleus, plastids and mitochondria. If we talk about human DNA, then it is called a chromosome. True, this is not entirely true, because chromosomes are a complex of chromatin and deoxyribonucleic acid.

Role in the cage

The main role of DNA in cells is the transmission of hereditary genes and the survival of future generations. Not only the external data of the future individual, but also its character and health depend on it. Deoxyribonucleic acid is in a supercoiled state, but for a quality life process it must be untwisted. Enzymes - topoisomerases and helicases help her with this.

Topoisomerases are nucleases, they are able to change the degree of twisting. Another of their functions is participation in transcription and replication (cell division). Helicases break hydrogen bonds between bases. There are ligase enzymes that “crosslink” broken bonds, and polymerases that are involved in the synthesis of new polynucleotide chains.

How DNA is deciphered

This abbreviation for biology is familiar. The full name of DNA is deoxyribonucleic acid. Not everyone can say this the first time, so DNA decoding is often omitted in speech. There is also the concept of RNA - ribonucleic acid, which consists of sequences of amino acids in proteins. They are directly linked, with RNA being the second most important macromolecule.

Human DNA

The human chromosomes within the nucleus are separated, making human DNA the most stable, complete information carrier. During genetic recombination, the helices are separated, sites are exchanged, and then the connection is restored. Due to DNA damage, new combinations and patterns are formed. The whole mechanism promotes natural selection. It is still unknown how long she is responsible for the transfer of the genome, and what is her metabolic evolution.

Who discovered

The first discovery of the structure of DNA is attributed to the English biologists James Watson and Francis Crick, who in 1953 revealed the structural features of the molecule. Found it in 1869, the Swiss physician Friedrich Miescher. He studied the chemical composition of animal cells with the help of leukocytes, which massively accumulate in purulent lesions.

Misher was studying ways to wash leukocytes, isolated proteins when he discovered that there was something else besides them. A flake sediment formed on the bottom of the dishes during processing. After examining these deposits under a microscope, the young doctor discovered the nuclei that remained after treatment with hydrochloric acid. It contained a compound that Friedrich called nuclein (from the Latin nucleus - nucleus).

MOSCOW, April 25 - RIA Novosti, Tatyana Pichugina. Exactly 65 years ago, British scientists James Watson and Francis Crick published an article on deciphering the structure of DNA, laying the foundations of a new science - molecular biology. This discovery changed a lot in the life of mankind. RIA Novosti talks about the properties of the DNA molecule and why it is so important.

In the second half of the 19th century, biology was a very young science. Scientists were just beginning to study the cell, and the concept of heredity, although already formulated by Gregor Mendel, was not widely accepted.

In the spring of 1868, a young Swiss doctor, Friedrich Miescher, arrived at the University of Tübingen (Germany) to do scientific work. He intended to find out what substances the cell consists of. For experiments, I chose leukocytes, which are easy to obtain from pus.

Separating the nucleus from protoplasm, proteins and fats, Misher discovered a compound with a high content of phosphorus. He called this molecule nuclein ("nucleus" in Latin - nucleus).

This compound exhibited acidic properties, hence the term "nucleic acid" was coined. Its prefix "deoxyribo" means that the molecule contains H-groups and sugars. Then it turned out that in fact it is salt, but the name was not changed.

At the beginning of the 20th century, scientists already knew that nuclein is a polymer (that is, a very long, flexible molecule of repeating units), the units are composed of four nitrogenous bases (adenine, thymine, guanine and cytosine), and nuclein is contained in chromosomes - compact structures that occur in dividing cells. Their ability to transmit hereditary traits was demonstrated by the American geneticist Thomas Morgan in experiments on Drosophila.

The model that explained genes

But what deoxyribonucleic acid, abbreviated DNA, does in the cell nucleus, was not understood for a long time. It was believed that it plays some structural role in the chromosomes. The units of heredity - genes - were attributed to the protein nature. The breakthrough was made by American researcher Oswald Avery, who experimentally proved that genetic material is transmitted from bacterium to bacterium through DNA.

It became clear that DNA needed to be studied. But how? At that time, only X-rays were available to scientists. To shine through biological molecules, they had to be crystallized, which is difficult. Deciphering the structure of protein molecules from X-ray patterns was carried out at the Cavendish Laboratory (Cambridge, UK). Young researchers working there, James Watson and Francis Crick, did not have their own experimental data on DNA, so they used x-rays of colleagues at King's College Maurice Wilkins and Rosalind Franklin.

Watson and Crick proposed a model of the structure of DNA that exactly matches X-ray patterns: two parallel strands are twisted into a right-handed helix. Each chain is made up of an arbitrary set of nitrogenous bases strung on a backbone of their sugars and phosphates, and held together by hydrogen bonds stretched between the bases. Moreover, adenine combines only with thymine, and guanine with cytosine. This rule is called the principle of complementarity.

Watson and Crick's model explained the four main functions of DNA: the replication of genetic material, its specificity, the storage of information in a molecule, and its ability to mutate.

The scientists published their discovery in the journal Nature on April 25, 1953. Ten years later, together with Maurice Wilkins, they were awarded the Nobel Prize in Biology (Rosalind Franklin died in 1958 from cancer at the age of 37).

“Now, more than half a century later, it can be stated that the discovery of the DNA structure played the same role in the development of biology as the discovery of the atomic nucleus in physics. The elucidation of the structure of the atom led to the birth of a new, quantum physics, and the discovery of the structure of DNA led to the birth of a new, molecular biology,” writes Maxim Frank-Kamenetsky, an outstanding geneticist, DNA researcher, author of the book “The Most Important Molecule”.

Genetic code

Now it remained to find out how this molecule works. DNA was known to contain instructions for the synthesis of cellular proteins that do all the work in the cell. Proteins are polymers made up of repeating sets (sequences) of amino acids. Moreover, there are only twenty amino acids. Animal species differ from each other in the set of proteins in the cells, that is, in different sequences of amino acids. Genetics argued that these sequences are set by genes, which, as it was then believed, serve as the first building blocks of life. But what genes are, no one really knew.

Clarity was introduced by the author of the theory of the Big Bang, physicist Georgy Gamov, an employee of the George Washington University (USA). Based on Watson and Crick's double-stranded DNA helix model, he suggested that a gene is a section of DNA, that is, a certain sequence of links - nucleotides. Since each nucleotide is one of the four nitrogenous bases, it's just a matter of finding out how four elements code for twenty. This was the idea behind the genetic code.

By the early 1960s, it was established that proteins are synthesized from amino acids in ribosomes - a kind of "factory" inside the cell. To start protein synthesis, an enzyme approaches DNA, recognizes a certain area at the beginning of the gene, synthesizes a copy of the gene in the form of a small RNA (it is called matrix), then a protein is grown from amino acids in the ribosome.

They also found out that the genetic code is three-letter. This means that three nucleotides correspond to one amino acid. The unit of code is called a codon. In the ribosome, information from mRNA is read codon by codon, sequentially. And each of them corresponds to several amino acids. What does the cipher look like?

This question was answered by Marshall Nirenberg and Heinrich Mattei from the USA. In 1961, they first reported their results at a biochemical congress in Moscow. By 1967, the genetic code had been completely deciphered. It turned out to be universal for all cells of all organisms, which had far-reaching consequences for science.

The discovery of the structure of DNA and the genetic code has completely reoriented biological research. The fact that each individual has a unique DNA sequence has dramatically changed forensic science. The deciphering of the human genome has given anthropologists a whole new way to study the evolution of our species. The recently invented CRISPR-Cas DNA editor has greatly advanced genetic engineering. Apparently, this molecule also stores the solution to the most pressing problems of mankind: cancer, genetic diseases, aging.

Nucleic acids are macromolecular substances consisting of mononucleotides, which are connected to each other in a polymer chain using 3",5" - phosphodiester bonds and packed in cells in a certain way.

Nucleic acids are biopolymers of two varieties: ribonucleic acid (RNA) and deoxyribonucleic acid (DNA). Each biopolymer consists of nucleotides that differ in carbohydrate residue (ribose, deoxyribose) and one of the nitrogenous bases (uracil, thymine). Accordingly, nucleic acids got their name.

Structure of deoxyribonucleic acid

Nucleic acids have primary, secondary and tertiary structures.

Primary structure of DNA

The primary structure of DNA is a linear polynucleotide chain in which the mononucleotides are connected by 3", 5" phosphodiester bonds. The starting material for assembling a nucleic acid chain in a cell is the nucleoside 5'-triphosphate, which, as a result of the removal of β and γ residues of phosphoric acid, is able to attach the 3'-carbon atom of another nucleoside. Thus, the 3" carbon atom of one deoxyribose covalently binds to the 5" carbon atom of another deoxyribose via a single phosphoric acid residue and forms a linear polynucleotide chain of nucleic acid. Hence the name: 3", 5"-phosphodiester bonds. Nitrogenous bases do not take part in the connection of nucleotides of one chain (Fig. 1.).

Such a connection, between the phosphoric acid molecule of one nucleotide and the carbohydrate of another, leads to the formation of a pentose-phosphate backbone of the polynucleotide molecule, on which nitrogenous bases are added one after the other from the side. Their sequence in the chains of nucleic acid molecules is strictly specific for cells of different organisms, i.e. has a specific character (Chargaff's rule).

A linear DNA chain, the length of which depends on the number of nucleotides included in the chain, has two ends: one is called the 3 "end and contains a free hydroxyl, and the other, the 5" end, contains a phosphoric acid residue. The circuit is polar and can be 5"->3" and 3"->5". An exception is circular DNA.

The genetic "text" of DNA is made up of code "words" - triplets of nucleotides called codons. DNA segments containing information about the primary structure of all types of RNA are called structural genes.

Polynucleoditic DNA chains reach gigantic sizes, so they are packed in a certain way in the cell.

Studying the composition of DNA, Chargaff (1949) established important regularities concerning the content of individual DNA bases. They helped uncover the secondary structure of DNA. These patterns are called Chargaff's rules. Chargaff rules the sum of purine nucleotides is equal to the sum of pyrimidine nucleotides, i.e. A + G / C + T \u003d 1 the content of adenine is equal to the content of thymine (A = T, or A / T = 1); the content of guanine is equal to the content of cytosine (G = C, or G/C = 1); the number of 6-amino groups is equal to the number of 6-keto groups of bases contained in DNA: G + T = A + C; only the sum of A + T and G + C is variable. If A + T > G-C, then this is the AT-type of DNA; if G + C > A + T, then this is the GC type of DNA. These rules say that when building DNA, a rather strict correspondence (pairing) must be observed not for purine and pyrimidine bases in general, but specifically for thymine with adenine and cytosine with guanine. Based on these rules, among other things, in 1953 Watson and Crick proposed a model of the secondary structure of DNA, called the double helix (Fig.).

Secondary structure of DNA

The secondary structure of DNA is a double helix, the model of which was proposed by D. Watson and F. Crick in 1953.

Prerequisites for creating a DNA model

As a result of initial analyzes, the idea was that DNA of any origin contains all four nucleotides in equal molar amounts. However, in the 1940s, E. Chargaff and his colleagues, as a result of the analysis of DNA isolated from various organisms, clearly showed that nitrogenous bases are contained in them in various quantitative ratios. Chargaff found that, although these ratios are the same for DNA from all cells of the same species of organisms, DNA from different species can differ markedly in the content of certain nucleotides. This suggested that the differences in the ratio of nitrogenous bases might be related to some biological code. Although the ratio of individual purine and pyrimidine bases in different DNA samples was not the same, when comparing the results of the analyzes, a certain pattern was revealed: in all samples, the total amount of purines was equal to the total amount of pyrimidines (A + G = T + C), the amount of adenine was equal to the amount of thymine (A = T), and the amount of guanine - the amount of cytosine (G = C). DNA isolated from mammalian cells was generally richer in adenine and thymine and relatively poorer in guanine and cytosine, while DNA from bacteria was richer in guanine and cytosine and relatively poorer in adenine and thymine. These data formed an important part of the factual material, on the basis of which the Watson-Crick DNA structure model was later built.

Another important indirect indication of the possible structure of DNA was L. Pauling's data on the structure of protein molecules. Pauling showed that several different stable configurations of the amino acid chain are possible in a protein molecule. One of the common configurations of the peptide chain - α-helix - is a regular helical structure. With such a structure, the formation of hydrogen bonds between amino acids located on adjacent turns of the chain is possible. Pauling described the α-helical configuration of the polypeptide chain in 1950 and suggested that DNA molecules also probably have a helical structure fixed by hydrogen bonds.

However, the most valuable information about the structure of the DNA molecule was provided by the results of X-ray diffraction analysis. X-rays, passing through a DNA crystal, undergo diffraction, that is, they are deflected in certain directions. The degree and nature of the deflection of the rays depend on the structure of the molecules themselves. The X-ray diffraction pattern (Fig. 3) gives the experienced eye a number of indirect indications regarding the structure of the molecules of the substance under study. Analysis of DNA X-ray diffraction patterns led to the conclusion that the nitrogenous bases (having a flat shape) are stacked like a stack of plates. X-ray patterns made it possible to identify three main periods in the structure of crystalline DNA: 0.34, 2, and 3.4 nm.

Watson-Crick DNA Model

Starting from Chargaff's analytical data, Wilkins' x-rays, and chemist's research, which provided information about the exact distances between atoms in a molecule, about the angles between the bonds of a given atom, and about the size of atoms, Watson and Crick began to build physical models of individual components of the DNA molecule at a certain scale. and "adjust" them to each other in such a way that the resulting system corresponds to various experimental data [show] .

Even earlier, it was known that adjacent nucleotides in a DNA chain are connected by phosphodiester bridges that link the 5'-carbon atom of deoxyribose of one nucleotide to the 3'-carbon atom of deoxyribose of the next nucleotide. Watson and Crick had no doubt that a period of 0.34 nm corresponds to the distance between successive nucleotides in a DNA strand. Further, it could be assumed that the period of 2 nm corresponds to the thickness of the chain. And in order to explain what real structure corresponds to a period of 3.4 nm, Watson and Crick, as well as Pauling earlier, assumed that the chain is twisted in the form of a spiral (or, more precisely, forms a helix, since the spiral in the strict sense of this the word is obtained when the turns form a conical rather than a cylindrical surface in space). Then the period of 3.4 nm will correspond to the distance between successive turns of this spiral. Such a spiral can be very dense or somewhat stretched, i.e., its turns can be flat or steep. Since the period of 3.4 nm is exactly 10 times the distance between consecutive nucleotides (0.34 nm), it is clear that each complete turn of the helix contains 10 nucleotides. From these data, Watson and Crick were able to calculate the density of a polynucleotide chain twisted into a helix with a diameter of 2 nm, with a distance between turns equal to 3.4 nm. It turned out that such a strand would have a density half that of the actual density of DNA, which was already known. I had to assume that the DNA molecule consists of two chains - that it is a double helix of nucleotides.

The next task was, of course, to elucidate the spatial relationship between the two strands forming the double helix. Having tried a number of strand arrangements on their physical model, Watson and Crick found that the best fit for all available data is one in which the two polynucleotide helices run in opposite directions; in this case, chains consisting of sugar and phosphate residues form the surface of a double helix, and purines and pyrimidines are located inside. The bases located opposite each other, belonging to two chains, are connected in pairs by hydrogen bonds; it is these hydrogen bonds that hold the chains together, thus fixing the overall configuration of the molecule.

The DNA double helix can be thought of as a helical rope ladder, with the rungs remaining horizontal. Then two longitudinal ropes will correspond to chains of sugar and phosphate residues, and the crossbars will correspond to pairs of nitrogenous bases connected by hydrogen bonds.

As a result of further study of possible models, Watson and Crick came to the conclusion that each "crossbar" should consist of one purine and one pyrimidine; at a period of 2 nm (corresponding to the diameter of the double helix), there would not be enough space for two purines, and the two pyrimidines could not be close enough together to form proper hydrogen bonds. An in-depth study of the detailed model showed that adenine and cytosine, making up a combination of the right size, still could not be located in such a way that hydrogen bonds formed between them. Similar reports also forced the guanine-thymine combination to be excluded, while the combinations adenine-thymine and guanine-cytosine were found to be quite acceptable. The nature of hydrogen bonds is such that adenine pairs with thymine, and guanine pairs with cytosine. This concept of specific base pairing made it possible to explain the "Chargaff rule", according to which in any DNA molecule the amount of adenine is always equal to the content of thymine, and the amount of guanine is always equal to the amount of cytosine. Two hydrogen bonds form between adenine and thymine, and three between guanine and cytosine. Due to this specificity in the formation of hydrogen bonds against each adenine in one chain, thymine is in the other; in the same way, only cytosine can be placed against each guanine. Thus, the chains are complementary to each other, that is, the sequence of nucleotides in one chain uniquely determines their sequence in the other. The two chains run in opposite directions and their phosphate end groups are at opposite ends of the double helix.

As a result of their research, in 1953 Watson and Crick proposed a model for the structure of the DNA molecule (Fig. 3), which remains relevant to the present. According to the model, a DNA molecule consists of two complementary polynucleotide chains. Each DNA strand is a polynucleotide consisting of several tens of thousands of nucleotides. In it, neighboring nucleotides form a regular pentose-phosphate backbone due to the combination of a phosphoric acid residue and deoxyribose by a strong covalent bond. The nitrogenous bases of one polynucleotide chain are arranged in a strictly defined order against the nitrogenous bases of the other. The alternation of nitrogenous bases in the polynucleotide chain is irregular.

The arrangement of nitrogenous bases in the DNA chain is complementary (from the Greek "complement" - addition), i.e. against adenine (A) is always thymine (T), and against guanine (G) - only cytosine (C). This is explained by the fact that A and T, as well as G and C, strictly correspond to each other, i.e. complement each other. This correspondence is given by the chemical structure of the bases, which allows the formation of hydrogen bonds in a pair of purine and pyrimidine. Between A and T there are two bonds, between G and C - three. These bonds provide partial stabilization of the DNA molecule in space. The stability of the double helix is ​​directly proportional to the number of G≡C bonds, which are more stable than the A=T bonds.

The known sequence of nucleotides in one strand of DNA makes it possible, by the principle of complementarity, to establish the nucleotides of another strand.

In addition, it has been established that nitrogenous bases having an aromatic structure are located one above the other in an aqueous solution, forming, as it were, a stack of coins. This process of forming stacks of organic molecules is called stacking. The polynucleotide chains of the DNA molecule of the considered Watson-Crick model have a similar physicochemical state, their nitrogenous bases are arranged in the form of a stack of coins, between the planes of which van der Waals interactions (stacking interactions) occur.

Hydrogen bonds between complementary bases (horizontally) and stacking interaction between base planes in a polynucleotide chain due to van der Waals forces (vertically) provide the DNA molecule with additional stabilization in space.

The sugar-phosphate backbones of both chains are turned outward, and the bases are inward, towards each other. The direction of the strands in DNA is antiparallel (one of them has the direction 5"->3", the other - 3"->5", i.e. the 3"-end of one strand is located opposite the 5"-end of the other.). The chains form right helixes with a common axis. One turn of the helix is ​​10 nucleotides, the size of the turn is 3.4 nm, the height of each nucleotide is 0.34 nm, the diameter of the helix is ​​2.0 nm. As a result of the rotation of one strand around the other, a major groove (about 20 Å in diameter) and a minor groove (about 12 Å) are formed in the DNA double helix. This form of the Watson-Crick double helix was later called the B-form. In cells, DNA usually exists in the B form, which is the most stable.

Functions of DNA

The proposed model explained many of the biological properties of deoxyribonucleic acid, including the storage of genetic information and the diversity of genes, provided by a wide variety of consecutive combinations of 4 nucleotides and the fact of the existence of a genetic code, the ability to self-reproduce and transmit genetic information, provided by the replication process, and the implementation of genetic information in the form of proteins, as well as any other compounds formed with the help of enzyme proteins.

Basic functions of DNA.

1. DNA is the carrier of genetic information, which is ensured by the fact of the existence of the genetic code.
2. Reproduction and transmitted genetic information in generations of cells and organisms. This function is provided by the replication process.
3. Implementation of genetic information in the form of proteins, as well as any other compounds formed with the help of enzyme proteins. This function is provided by the processes of transcription and translation.

Forms of organization of double-stranded DNA

DNA can form several types of double helixes (Fig. 4). Currently, six forms are already known (from A to E and Z-form).

Structural forms of DNA, as established by Rosalind Franklin, depend on the saturation of the nucleic acid molecule with water. In studies of DNA fibers using X-ray diffraction analysis, it was shown that the X-ray diffraction pattern radically depends on at what relative humidity, at what degree of water saturation of this fiber the experiment takes place. If the fiber was sufficiently saturated with water, then one radiograph was obtained. When dried, a completely different X-ray pattern appeared, very different from the X-ray pattern of a high-moisture fiber.

Molecule of high humidity DNA is called B-shape. Under physiological conditions (low salt concentration, high degree of hydration), the dominant structural type of DNA is the B-form (the main form of double-stranded DNA is the Watson-Crick model). The helix pitch of such a molecule is 3.4 nm. There are 10 complementary pairs per turn in the form of twisted stacks of "coins" - nitrogenous bases. The stacks are held together by hydrogen bonds between two opposite "coins" of the stacks, and are "coiled" with two ribbons of the phosphodiester backbone twisted into a right-handed helix. The planes of the nitrogenous bases are perpendicular to the axis of the helix. Neighboring complementary pairs are rotated relative to each other by 36°. The helix diameter is 20Å, with the purine nucleotide occupying 12Å and the pyrimidine nucleotide occupying 8Å.

DNA molecule of lower moisture is called A-form. The A-form is formed under conditions of less high hydration and at a higher content of Na + or K + ions. This wider right-handed conformation has 11 base pairs per turn. The planes of nitrogenous bases have a stronger inclination to the axis of the helix, they deviate from the normal to the axis of the helix by 20°. This implies the presence of an internal void with a diameter of 5 Å. The distance between adjacent nucleotides is 0.23 nm, the length of the coil is 2.5 nm, and the diameter of the helix is ​​2.3 nm.

Initially, the A-form of DNA was thought to be less important. However, later it turned out that the A-form of DNA, as well as the B-form, is of great biological importance. The RNA-DNA helix in the template-seed complex has the A-form, as well as the RNA-RNA helix and RNA hairpin structures (the 2'-hydroxyl group of ribose does not allow RNA molecules to form the B-form). The A-form of DNA is found in spores. It has been established that the A-form of DNA is 10 times more resistant to UV rays than the B-form.

The A-form and B-form are called the canonical forms of DNA.

Forms C-E also right-handed, their formation can only be observed in special experiments, and, apparently, they do not exist in vivo. The C-form of DNA has a structure similar to B-DNA. The number of base pairs per turn is 9.33, and the length of the helix is ​​3.1 nm. The base pairs are inclined at an angle of 8 degrees relative to the perpendicular position to the axis. The grooves are close in size to the grooves of B-DNA. In this case, the main groove is somewhat smaller, and the minor groove is deeper. Natural and synthetic DNA polynucleotides can pass into the C-form.

Table 1. Characteristics of some types of DNA structures
Spiral type	A	B	Z
Spiral pitch	0.32 nm	3.38 nm	4.46 nm
Spiral twist	Right	Right	Left
Number of base pairs per turn	11	10	12
Distance between base planes	0.256 nm	0.338 nm	0.371 nm
Glycosidic bond conformation	anti	anti	anti-C syn-G
Furanose ring conformation	C3 "-endo	C2 "-endo	C3 "-endo-G C2 "-endo-C
Groove width, small/large	1.11/0.22 nm	0.57/1.17 nm	0.2/0.88 nm
Groove depth, small/large	0.26/1.30 nm	0.82/0.85 nm	1.38/0.37 nm
Spiral diameter	2.3 nm	2.0 nm	1.8 nm

Structural elements of DNA
(non-canonical DNA structures)

Structural elements of DNA include unusual structures limited by some special sequences:

Z-form of DNA - is formed in places of the B-form of DNA, where purines alternate with pyrimidines or in repeats containing methylated cytosine. Palindromes are flip sequences, inverted repeats of base sequences, having a second-order symmetry with respect to two DNA strands and forming "hairpins" and "crosses". The H-form of DNA and triple helixes of DNA are formed in the presence of a site containing only purines in one strand of the normal Watson-Crick duplex, and in the second strand, respectively, pyrimidines complementary to them. G-quadruplex (G-4) is a four-stranded DNA helix, where 4 guanine bases from different strands form G-quartets (G-tetrads), held together by hydrogen bonds to form G-quadruplexes.

Z-form of DNA was discovered in 1979 while studying the hexanucleotide d(CG)3 - . It was opened by MIT professor Alexander Rich and his staff. The Z-form has become one of the most important structural elements of DNA due to the fact that its formation was observed in DNA regions where purines alternate with pyrimidines (for example, 5'-HCHCHC-3'), or in repeats 5'-CHCHCH-3' containing methylated cytosine. An essential condition for the formation and stabilization of Z-DNA was the presence in it of purine nucleotides in the syn-conformation, alternating with pyrimidine bases in the anti-conformation.

Natural DNA molecules mostly exist in the right B form unless they contain sequences like (CG)n. However, if such sequences are part of DNA, then these regions, when the ionic strength of the solution or cations that neutralize the negative charge on the phosphodiester backbone, can change into the Z-form, while other DNA regions in the chain remain in the classical B-form. The possibility of such a transition indicates that the two strands in the DNA double helix are in a dynamic state and can unwind relative to each other, passing from the right form to the left one and vice versa. The biological consequences of this lability, which allows conformational transformations of the DNA structure, are not yet fully understood. It is believed that Z-DNA regions play a role in the regulation of the expression of certain genes and take part in genetic recombination.

The Z-form of DNA is a left-handed double helix, in which the phosphodiester backbone is zigzag along the axis of the molecule. Hence the name of the molecule (zigzag)-DNA. Z-DNA is the least twisted (12 base pairs per turn) and thinnest known in nature. The distance between adjacent nucleotides is 0.38 nm, the coil length is 4.56 nm, and the Z-DNA diameter is 1.8 nm. In addition, the appearance of this DNA molecule is distinguished by the presence of a single groove.

The Z-form of DNA has been found in prokaryotic and eukaryotic cells. To date, antibodies have been obtained that can distinguish between the Z-form and the B-form of DNA. These antibodies bind to specific regions of the giant chromosomes of Drosophila (Dr. melanogaster) salivary gland cells. The binding reaction is easy to follow due to the unusual structure of these chromosomes, in which denser regions (disks) contrast with less dense regions (interdisks). Z-DNA regions are located in the interdiscs. It follows from this that the Z-form actually exists in natural conditions, although the sizes of the individual sections of the Z-form are not yet known.

(shifters) - the most famous and frequently occurring base sequences in DNA. A palindrome is a word or phrase that reads from left to right and vice versa in the same way. Examples of such words or phrases are: HUT, COSSACK, FLOOD, AND A ROSE FALLED ON AZOR'S PAWS. When applied to sections of DNA, this term (palindrome) means the same alternation of nucleotides along the chain from right to left and from left to right (like the letters in the word "hut", etc.).

A palindrome is characterized by the presence of inverted repeats of base sequences having a second-order symmetry with respect to two DNA strands. Such sequences, for obvious reasons, are self-complementary and tend to form hairpin or cruciform structures (Fig.). Hairpins help regulatory proteins to recognize the place where the genetic text of chromosome DNA is copied.

In cases where an inverted repeat is present in the same DNA strand, such a sequence is called a mirror repeat. Mirror repeats do not have self-complementary properties and therefore are not capable of forming hairpin or cruciform structures. Sequences of this type are found in almost all large DNA molecules and can range from just a few base pairs to several thousand base pairs.

The presence of palindromes in the form of cruciform structures in eukaryotic cells has not been proven, although a number of cruciform structures have been found in vivo in E. coli cells. The presence of self-complementary sequences in RNA or single-stranded DNA is the main reason for the folding of the nucleic chain in solutions into a certain spatial structure, characterized by the formation of many "hairpins".

H-form of DNA- this is a helix that is formed by three strands of DNA - the triple helix of DNA. It is a complex of the Watson-Crick double helix with the third single-stranded DNA strand, which fits into its large groove, with the formation of the so-called Hoogsteen pair.

The formation of such a triplex occurs as a result of the addition of the DNA double helix in such a way that half of its section remains in the form of a double helix, and the second half is disconnected. In this case, one of the disconnected spirals forms a new structure with the first half of the double helix - a triple helix, and the second turns out to be unstructured, in the form of a single-filament section. A feature of this structural transition is a sharp dependence on the pH of the medium, the protons of which stabilize the new structure. Due to this feature, the new structure was called the H-form of DNA, the formation of which was found in supercoiled plasmids containing homopurine-homopyrimidine regions, which are a mirror repeat.

In further studies, the possibility of structural transition of some homopurine-homopyrimidine double-stranded polynucleotides was established with the formation of a three-stranded structure containing:

• one homopurine and two homopyrimidine strands ( Py-Pu-Py triplex) [Hoogsteen interaction].

  The constituent blocks of the Py-Pu-Py triplex are canonical isomorphic CGC+ and TAT triads. Stabilization of the triplex requires protonation of the CGC+ triad, so these triplexes are dependent on the pH of the solution.

• one homopyrimidine and two homopurine strands ( Py-Pu-Pu triplex) [inverse Hoogsteen interaction].

  The constituent blocks of the Py-Pu-Pu triplex are the canonical isomorphic CGG and TAA triads. An essential property of Py-Pu-Pu triplexes is the dependence of their stability on the presence of doubly charged ions, and different ions are needed to stabilize triplexes of different sequences. Since the formation of Py-Pu-Pu triplexes does not require protonation of their constituent nucleotides, such triplexes can exist at neutral pH.

  Note: the direct and reverse Hoogsteen interaction is explained by the symmetry of 1-methylthymine: a 180 ° rotation leads to the fact that the place of the O4 atom is occupied by the O2 atom, while the system of hydrogen bonds is preserved.

There are two types of triple helixes:

1. parallel triple helixes in which the polarity of the third strand is the same as that of the homopurine chain of the Watson-Crick duplex
2. antiparallel triple helixes, in which the polarities of the third and homopurine chains are opposite.

Chemically homologous chains in both Py-Pu-Pu and Py-Pu-Py triplexes are in antiparallel orientation. This was further confirmed by NMR spectroscopy data.

G-quadruplex- 4-stranded DNA. Such a structure is formed if there are four guanines, which form the so-called G-quadruplex - a round dance of four guanines.

The first hints of the possibility of the formation of such structures were obtained long before the breakthrough work of Watson and Crick - as early as 1910. Then the German chemist Ivar Bang discovered that one of the components of DNA - guanosic acid - forms gels at high concentrations, while other components of DNA do not have this property.

In 1962, using the X-ray diffraction method, it was possible to establish the cell structure of this gel. It turned out to be composed of four guanine residues, linking each other in a circle and forming a characteristic square. In the center, the bond is supported by a metal ion (Na, K, Mg). The same structures can be formed in DNA if it contains a lot of guanine. These flat squares (G-quartets) are stacked to form fairly stable, dense structures (G-quadruplexes).

Four separate strands of DNA can be woven into four-stranded complexes, but this is rather an exception. More often, a single strand of nucleic acid is simply tied into a knot, forming characteristic thickenings (for example, at the ends of chromosomes), or double-stranded DNA forms a local quadruplex at some guanine-rich site.

The most studied is the existence of quadruplexes at the ends of chromosomes - on telomeres and in oncopromoters. However, a complete understanding of the localization of such DNA in human chromosomes is still not known.

All these unusual structures of DNA in the linear form are unstable compared to the B-form of DNA. However, DNA often exists in a ring form of topological tension when it has what is known as supercoiling. Under these conditions, non-canonical DNA structures are easily formed: Z-forms, "crosses" and "hairpins", H-forms, guanine quadruplexes, and the i-motif.

• Supercoiled form - noted when released from the cell nucleus without damage to the pentose-phosphate backbone. It has the form of supertwisted closed rings. In the supertwisted state, the DNA double helix is ​​"twisted on itself" at least once, i.e. it contains at least one supercoil (takes the shape of a figure eight).
• Relaxed state of DNA - observed with a single break (break of one strand). In this case, the supercoils disappear and the DNA takes the form of a closed ring.
• The linear form of DNA is observed when two strands of the double helix are broken.

All three listed forms of DNA are easily separated by gel elecrophoresis.

Tertiary structure of DNA

Tertiary structure of DNA is formed as a result of additional twisting in space of a double-stranded molecule - its supercoiling. Supercoiling of the DNA molecule in eukaryotic cells, in contrast to prokaryotes, is carried out in the form of complexes with proteins.

Almost all eukaryotic DNA is located in the chromosomes of the nuclei, only a small amount of it is found in mitochondria, and in plants and in plastids. The main substance of the chromosomes of eukaryotic cells (including human chromosomes) is chromatin, consisting of double-stranded DNA, histone and non-histone proteins.

Histone proteins of chromatin

Histones are simple proteins that make up up to 50% of chromatin. In all the studied cells of animals and plants, five main classes of histones were found: H1, H2A, H2B, H3, H4, differing in size, amino acid composition and charge (always positive).

Mammalian histone H1 consists of a single polypeptide chain containing approximately 215 amino acids; the sizes of other histones vary from 100 to 135 amino acids. All of them are spiralized and twisted into a globule with a diameter of about 2.5 nm, contain an unusually large amount of positively charged amino acids lysine and arginine. Histones can be acetylated, methylated, phosphorylated, poly(ADP)-ribosylated, and histones H2A and H2B can be covalently linked to ubiquitin. What is the role of such modifications in the formation of the structure and performance of functions by histones has not yet been fully elucidated. It is assumed that this is their ability to interact with DNA and provide one of the mechanisms for regulating the action of genes.

Histones interact with DNA mainly through ionic bonds (salt bridges) formed between the negatively charged phosphate groups of DNA and the positively charged lysine and arginine residues of histones.

Non-histone proteins of chromatin

Non-histone proteins, unlike histones, are very diverse. Up to 590 different fractions of DNA-binding nonhistone proteins have been isolated. They are also called acidic proteins, since acidic amino acids predominate in their structure (they are polyanions). The specific regulation of chromatin activity is associated with a variety of non-histone proteins. For example, enzymes essential for DNA replication and expression can bind to chromatin transiently. Other proteins, say those involved in various regulatory processes, bind to DNA only in specific tissues or at certain stages of differentiation. Each protein is complementary to a specific sequence of DNA nucleotides (DNA site). This group includes:

• a family of site-specific zinc finger proteins. Each "zinc finger" recognizes a specific site consisting of 5 nucleotide pairs.
• a family of site-specific proteins - homodimers. A fragment of such a protein in contact with DNA has a "helix-turn-helix" structure.
• high mobility proteins (HMG proteins - from English, high mobility gel proteins) are a group of structural and regulatory proteins that are constantly associated with chromatin. They have a molecular weight of less than 30 kD and are characterized by a high content of charged amino acids. Due to their low molecular weight, HMG proteins are highly mobile during polyacrylamide gel electrophoresis.
• enzymes of replication, transcription and repair.

With the participation of structural, regulatory proteins and enzymes involved in the synthesis of DNA and RNA, the nucleosome thread is converted into a highly condensed complex of proteins and DNA. The resulting structure is 10,000 times shorter than the original DNA molecule.

Chromatin

Chromatin is a complex of proteins with nuclear DNA and inorganic substances. Most of the chromatin is inactive. It contains densely packed, condensed DNA. This is heterochromatin. There are constitutive, genetically inactive chromatin (satellite DNA) consisting of non-expressed regions, and facultative - inactive in a number of generations, but under certain circumstances capable of expressing.

Active chromatin (euchromatin) is uncondensed, i.e. packed less tightly. In different cells, its content ranges from 2 to 11%. In the cells of the brain, it is the most - 10-11%, in the cells of the liver - 3-4 and kidneys - 2-3%. There is an active transcription of euchromatin. At the same time, its structural organization makes it possible to use the same DNA genetic information inherent in a given type of organism in different ways in specialized cells.

In an electron microscope, the image of chromatin resembles beads: spherical thickenings about 10 nm in size, separated by filamentous bridges. These spherical thickenings are called nucleosomes. The nucleosome is the structural unit of chromatin. Each nucleosome contains a 146 bp long supercoiled DNA segment wound to form 1.75 left turns per nucleosome core. The nucleosomal core is a histone octamer consisting of H2A, H2B, H3, and H4 histones, two molecules of each type (Fig. 9), which looks like a disk 11 nm in diameter and 5.7 nm thick. The fifth histone, H1, is not part of the nucleosomal core and is not involved in the process of DNA winding around the histone octamer. It contacts DNA at the points where the double helix enters and exits the nucleosomal core. These are intercore (linker) sections of DNA, the length of which varies depending on the type of cell from 40 to 50 nucleotide pairs. As a result, the length of the DNA fragment that is part of the nucleosomes also varies (from 186 to 196 nucleotide pairs).

The nucleosome contains about 90% of DNA, the rest of it is the linker. It is believed that nucleosomes are fragments of "silent" chromatin, while the linker is active. However, nucleosomes can unfold and become linear. Unfolded nucleosomes are already active chromatin. This clearly shows the dependence of the function on the structure. It can be assumed that the more chromatin is in the composition of globular nucleosomes, the less active it is. Obviously, in different cells the unequal proportion of resting chromatin is associated with the number of such nucleosomes.

On electron microscopic photographs, depending on the conditions of isolation and the degree of stretching, chromatin can look not only as a long thread with thickenings - "beads" of nucleosomes, but also as a shorter and denser fibril (fiber) with a diameter of 30 nm, the formation of which is observed during the interaction histone H1 associated with the linker region of DNA and histone H3, which leads to additional twisting of the helix of six nucleosomes per turn with the formation of a solenoid with a diameter of 30 nm. In this case, the histone protein can interfere with the transcription of a number of genes and thus regulate their activity.

As a result of the interactions of DNA with histones described above, a segment of the DNA double helix of 186 base pairs with an average diameter of 2 nm and a length of 57 nm turns into a helix with a diameter of 10 nm and a length of 5 nm. With the subsequent compression of this helix to a fiber with a diameter of 30 nm, the degree of condensation increases by another six times.

Ultimately, the packaging of the DNA duplex with five histones results in a 50-fold DNA condensation. However, even such a high degree of condensation cannot explain the almost 50,000-100,000-fold DNA compaction in the metaphase chromosome. Unfortunately, the details of the further packing of chromatin up to the metaphase chromosome are not yet known; therefore, only general features of this process can be considered.

Levels of DNA compaction in chromosomes

Each DNA molecule is packaged into a separate chromosome. Diploid human cells contain 46 chromosomes, which are located in the cell nucleus. The total length of the DNA of all the chromosomes of a cell is 1.74 m, but the diameter of the nucleus in which the chromosomes are packed is millions of times smaller. Such compact packing of DNA in chromosomes and chromosomes in the cell nucleus is provided by a variety of histone and non-histone proteins interacting in a certain sequence with DNA (see above). Compaction of DNA in chromosomes makes it possible to reduce its linear dimensions by about 10,000 times - conditionally from 5 cm to 5 microns. There are several levels of compactization (Fig. 10).

• DNA double helix is ​​a negatively charged molecule with a diameter of 2 nm and a length of several cm.
• nucleosomal level- chromatin looks in an electron microscope as a chain of "beads" - nucleosomes - "on a thread". The nucleosome is a universal structural unit that is found both in euchromatin and heterochromatin, in the interphase nucleus and metaphase chromosomes.

  The nucleosomal level of compaction is provided by special proteins - histones. Eight positively charged histone domains form the core (core) of the nucleosome around which the negatively charged DNA molecule is wound. This gives a shortening by a factor of 7, while the diameter increases from 2 to 11 nm.

• solenoid level

  The solenoid level of chromosome organization is characterized by the twisting of the nucleosomal filament and the formation of thicker fibrils 20-35 nm in diameter from it - solenoids or superbids. The solenoid pitch is 11 nm, and there are about 6-10 nucleosomes per turn. Solenoid packing is considered more probable than superbid packing, according to which a chromatin fibril with a diameter of 20–35 nm is a chain of granules, or superbids, each of which consists of eight nucleosomes. At the solenoid level, the linear size of DNA is reduced by 6-10 times, the diameter increases to 30 nm.

• loop level

  The loop level is provided by non-histone site-specific DNA-binding proteins that recognize and bind to specific DNA sequences, forming loops of approximately 30-300 kb. The loop ensures gene expression, i.e. the loop is not only a structural, but also a functional formation. Shortening at this level occurs by 20-30 times. The diameter increases to 300 nm. Loop-like "lampbrush" structures in amphibian oocytes can be seen on cytological preparations. These loops appear to be supercoiled and represent DNA domains, probably corresponding to units of chromatin transcription and replication. Specific proteins fix the bases of the loops and, possibly, some of their internal regions. The loop-like domain organization facilitates the folding of chromatin in metaphase chromosomes into helical structures of higher orders.

• domain level

  The domain level of chromosome organization has not been studied enough. At this level, the formation of loop domains is noted - structures of filaments (fibrils) 25-30 nm thick, which contain 60% protein, 35% DNA and 5% RNA, are practically invisible in all phases of the cell cycle with the exception of mitosis and are somewhat randomly distributed over cell nucleus. Loop-like "lampbrush" structures in amphibian oocytes can be seen on cytological preparations.

  Loop domains are attached with their base to the intranuclear protein matrix in the so-called built-in attachment sites, often referred to as MAR / SAR sequences (MAR, from the English matrix associated region; SAR, from the English scaffold attachment regions) - DNA fragments several hundred long base pairs that are characterized by a high content (>65%) of A/T base pairs. Each domain appears to have a single origin of replication and functions as an autonomous supercoiled unit. Any loop domain contains many transcription units, the functioning of which is likely to be coordinated - the entire domain is either in an active or inactive state.

  At the domain level, as a result of sequential packing of chromatin, the linear dimensions of DNA decrease by about 200 times (700 nm).

• chromosome level

  At the chromosomal level, the prophase chromosome condenses into a metaphase one with the compaction of loop domains around the axial framework of non-histone proteins. This supercoiling is accompanied by phosphorylation of all H1 molecules in the cell. As a result, the metaphase chromosome can be depicted as densely packed solenoid loops coiled into a tight spiral. A typical human chromosome can contain up to 2600 loops. The thickness of such a structure reaches 1400 nm (two chromatids), while the DNA molecule is shortened by 104 times, i.e. from 5 cm stretched DNA to 5 µm.

Functions of chromosomes

In interaction with extrachromosomal mechanisms, chromosomes provide

1. storage of hereditary information
2. using this information to create and maintain cellular organization
3. regulation of reading hereditary information
4. self-duplication of genetic material
5. the transfer of genetic material from a mother cell to daughter cells.

There is evidence that upon activation of a chromatin region, i.e. during transcription, histone H1 is reversibly removed from it first, and then the histone octet. This causes decondensation of chromatin, the successive transition of a 30-nm chromatin fibril into a 10-nm filament and its further unfolding into free DNA regions, i.e. loss of nucleosomal structure.

Almost everyone has heard about the existence of DNA molecules in living cells and knows that this molecule is responsible for the transmission of hereditary information. A huge bunch of different films, to one degree or another, build their plots on the properties of a small, but proud, very important molecule.

However, few people can at least approximately explain what exactly is part of the DNA molecule and how the processes of reading all this information about the “structure of the whole organism” function. Only a few are able to read “deoxyribonucleic acid” without hesitation.

Let's try to figure out what it consists of and what it looks like the most important molecule for each of us.

The structure of the structural link - nucleotide

The composition of the DNA molecule includes many structural units, since it is a biopolymer. A polymer is a macromolecule that consists of many small repeating fragments connected in series. Just like a chain is made up of links.

The structural unit of the DNA macromolecule is the nucleotide. The composition of the nucleotides of the DNA molecule includes the remains of three substances - phosphoric acid, saccharide (deoxyribose) and one of the four possible nitrogen-containing bases.

The composition of the DNA molecule includes nitrogenous bases: adenine (A), guanine (G), cytosine (C) and thymine (T).

The composition of the nucleotide chain is displayed by the alternation of the bases included in it: -AAGCGTTAGCACGT-, etc. The sequence can be any. This forms a single strand of DNA.

Helical molecule. The phenomenon of complementarity

The size of the human DNA molecule is monstrously huge (on the scale of other molecules, of course)! The genome of a single cell (46 chromosomes) contains approximately 3.1 billion base pairs. The length of the DNA chain, composed of such a number of links, is approximately two meters. It is difficult to imagine how such a bulky molecule can be placed within a tiny cell.

But nature took care of a more compact package and protection of its genome - two chains are interconnected by nitrogenous bases and form a well-known double helix. Thus, it is possible to reduce the length of the molecule by almost six times.

The order of interaction of nitrogenous bases is strictly determined by the phenomenon of complementarity. Adenine can only bind to thymine, while cytosine can only bind to guanine. These complementary pairs fit together like a key and lock, like puzzle pieces.

Now let's calculate how much memory in a computer (well, or on a flash drive) all the information about this small (on the scale of our world) molecule should occupy. The number of base pairs is 3.1x10 9 . There are 4 values ​​in total, which means that 2 bits of information are enough for one pair (2 2 values). We multiply all this by each other and we get 6200000000 bits, or 775000000 bytes, or 775000 kilobytes, or 775 megabytes. Which roughly corresponds to the capacity of a CD disc or the volume of some 40-minute film series in average quality.

Chromosome formation. Determination of the human genome

In addition to spiralization, the molecule is repeatedly subjected to compaction. The double helix begins to twist like a ball of thread - this process is called supercoiling and occurs with the help of a special histone protein, on which the chain is wound like a coil.

This process reduces the length of the molecule by another 25-30 times. Being subjected to several more levels of packaging, more and more compacted, one DNA molecule, together with auxiliary proteins, forms a chromosome.

All information that concerns the form, type and features of the functioning of our body is determined by a set of genes. A gene is a strictly defined section of a DNA molecule. It consists of an unchanged sequence of nucleotides. Moreover, the gene is rigidly determined not only by its composition, but also by its position relative to other parts of the chain.

Ribonucleic acid and its role in protein synthesis

In addition to DNA, there are other types of nucleic acids - messenger, transport and ribosomal RNA (ribonucleic acid). RNA chains are much smaller and shorter, which makes them able to penetrate the nuclear membrane.

The RNA molecule is also a biopolymer. Its structural fragments are similar to those that are part of DNA with a small exception of the saccharide (ribose instead of deoxyribose). There are four types of nitrogenous bases: familiar to us A, G, C and uracil (U) instead of thymine. The picture above shows all this clearly.

A DNA macromolecule is capable of transmitting information to RNA in an untwisted form. The unwinding of the helix occurs with the help of a special enzyme that separates the double helix into separate chains - like the halves of a zipper lock.

At the same time, a complementary RNA chain is created parallel to the DNA chain. After copying the information and getting from the nucleus into the environment of the cell, the RNA chain initiates the processes of synthesis of the protein encoded by the gene. Protein synthesis takes place in special cell organelles - ribosomes.

The ribosome, as it reads the chain, determines in which sequence the amino acids must be connected, one after the other - as information is read into the RNA. Then, the synthesized chain of amino acids takes a certain 3D shape.

This voluminous structural molecule is a protein capable of performing the encoded functions of enzymes, hormones, receptors and building material.

conclusions

For any living being, it is protein (protein) that is the end product of each gene. It is proteins that determine all the variety of forms, properties and qualities that are encrypted in our cells.

Dear blog readers, do you know where the DNA is, leave comments or reviews that you would like to know. Someone will find this very useful!