Central dogma of molecular biology. The history of the term "dogma"

In order not only to understand the significance of the structural features of the cell, but also, most importantly, to understand the functional functions of its individual components and the whole cell as a whole, in order to combine the study of cell morphology with the main biochemical and genetic features of its structure and work, in order to study the cell precisely with positions of modern cell biology, it is necessary to at least briefly recall the main molecular biological patterns, once again briefly refer to the content of the central dogma molecular biology.

The cell as such performs many different functions. As we have already said, some of them are general cellular, some are special, characteristic of special cell types. The main working mechanisms for these functions are proteins or their complexes with other biological macromolecules such as nucleic acids, lipids and polysaccharides. For example, it is known that the processes of transport in the cell of various substances, from ions to macromolecules, are determined by the work of special proteins or lipoprotein complexes that are part of the plasma and other cell membranes. Almost all processes of synthesis, decay, rearrangement of various proteins, nucleic acids, lipids, carbohydrates occur as a result of the activity of protein-enzymes specific for each individual reaction. Syntheses of individual biological monomers, nucleotides, amino acids, fatty acids, sugars and other compounds are also carried out by a huge number of specific enzymes - proteins. Contraction, which leads to cell mobility or to the movement of substances and structures inside cells, is also carried out by special contractile proteins. Many cell reactions in response to external factors (viruses, hormones, foreign proteins, etc.) begin with the interaction of these factors with special cellular receptor proteins.

Proteins are the main components of almost all cellular structures. A bunch of chemical reactions inside the cell is determined by many enzymes, each of which leads one or more separate reactions. The structure of each individual protein is strictly specific, which is expressed in the specificity of their primary structure - in the sequence of amino acids along the polypeptide, protein chain. Moreover, the specificity of this amino acid sequence is unmistakably repeated in all molecules of this cellular protein.

Such correctness in reproducing an unambiguous sequence of amino acids in a protein chain is determined by the DNA structure of that gene region, which is ultimately responsible for the structure and synthesis of this protein. These ideas serve as the main postulate of molecular biology, its "dogma". Information about the future protein molecule is transmitted to the sites of its synthesis (into ribosomes) by an intermediary - messenger RNA (mRNA), the nucleotide composition of which reflects the composition and nucleotide sequence of the DNA gene region. A polypeptide chain is built in the ribosome, the sequence of amino acids in which is determined by the sequence of nucleotides in mRNA, the sequence of their triplets. Thus, the central dogma of molecular biology emphasizes the unidirectional transmission of information: only from DNA to protein with the help of an intermediate - mRNA (DNA → mRNA → protein). For some RNA-containing viruses, the chain of information transfer can follow the scheme RNA → mRNA → protein. This does not change the essence of the matter, since the determining link here is also the nucleic acid. The reverse pathways of determination from protein to nucleic acid, to DNA or RNA are unknown.

In order to proceed further to the study of cell structures associated with all stages of protein synthesis, we need to briefly dwell on the main processes and components that determine this phenomenon.

Currently based on contemporary ideas about the biosynthesis of proteins, we can give the following general schematic diagram of this complex and multi-stage process (Fig. 16).

The main, "command" role in determining the specific structure of proteins belongs to deoxyribonucleic acid - DNA. The DNA molecule is an extremely long linear structure consisting of two intertwisted polymer chains. The constituent elements - monomers - of these chains are four types of deoxyribonucleotides, the alternation or sequence of which along the chain is unique and specific for each DNA molecule and each of its sections. Different sufficiently long sections of the DNA molecule are responsible for the synthesis of different proteins. Thus, one DNA molecule can determine the synthesis a large number functionally and chemically different cell proteins. For the synthesis of each one type of protein, only a certain section of the DNA molecule is responsible. Such a region of the DNA molecule, associated with the synthesis of one particular protein in the cell, is often referred to by the term "cistron". Currently, the concept of cistron is considered as equivalent to the concept of gene. The unique structure of a gene - in a certain sequential arrangement of its nucleotides along the chain - contains all the information about the structure of one corresponding protein.

From general scheme protein synthesis, it can be seen (see Fig. 16) that the starting point from which the flow of information for the biosynthesis of proteins in the cell begins is DNA. Consequently, it is DNA that contains the primary record of information that must be preserved and reproduced from cell to cell, from generation to generation.

Briefly addressing the issue of storage genetic information, i.e. about the localization of DNA in the cell, we can say the following. It has long been known that, unlike all other components of the protein-synthesizing apparatus, DNA has a special, very limited localization: its location in the cells of higher (eukaryotic) organisms will be the cell nucleus. In lower (prokaryotic) organisms that do not have a well-formed cell nucleus, DNA is also mixed from the rest of the protoplasm in the form of one or more compact nucleotide formations. In full accordance with this, the nucleus of eukaryotes or the nucleoid of prokaryotes has long been considered as a receptacle for genes, as a unique cellular organelle that controls the implementation of the hereditary traits of organisms and their transmission in generations.

The main principle underlying the macromolecular structure of DNA is the so-called principle of complementarity (Fig. 17). As already mentioned, the DNA molecule consists of two intertwisted chains. These chains are linked to each other through the interaction of their opposite nucleotides. At the same time, for structural reasons, the existence of such a double-stranded structure is possible only if the opposite nucleotides of both chains are sterically complementary, i.e. will be their spatial structure complement each other. Such complementary - complementary - pairs of nucleotides are couple A-T(adenine-thymine) and a pair of G-C (guanine-cytosine).

Therefore, according to this principle of complementarity, if in one strand of a DNA molecule we have a certain sequence of four types of nucleotides, then in the second strand the sequence of nucleotides will be uniquely determined, so that each A of the first strand will correspond to T in the second strand, each T of the first strand - A in the second chain, each G of the first chain - C in the second chain and each C of the first chain - G in the second chain.

This structural principle underlying the double-stranded structure of the DNA molecule makes it easy to understand the exact reproduction of the original structure, i.e. accurate reproduction of information recorded in the chains of a molecule in the form of a specific sequence of four types of nucleotides. Indeed, the synthesis of new DNA molecules in a cell occurs only on the basis of existing DNA molecules. In this case, the two chains of the original DNA molecule begin to diverge from one of the ends, and on each of the separated single-stranded sections, the second chain begins to assemble from the free nucleotides present in the medium in strict accordance with the principle of complementarity. The process of divergence of the two strands of the original DNA molecule continues, and accordingly both strands are supplemented with complementary strands. As a result (as can be seen in Fig. 17), two DNA molecules appear instead of one, exactly identical to the original. In each resulting "daughter" DNA molecule, one strand is entirely derived from the original, and the other is newly synthesized.

It must be emphasized that the potential for exact reproduction is inherent in the double-stranded complementary structure of DNA as such, and the discovery of this, of course, is one of the main achievements of biology.

However, the problem of reproduction (reduplication) of DNA is not limited to a statement of the potential ability of its structure to accurately reproduce its own nucleotide sequence. The fact is that DNA itself is not a self-reproducing molecule at all. For the implementation of the synthesis process - DNA reproduction according to the scheme described above - the activity of a special enzymatic complex called DNA polymerase is necessary. It is this enzyme that sequentially proceeds from one end of the DNA molecule to the other, the process of separating two strands with simultaneous polymerization of free nucleotides on them according to the complementary principle. Thus, DNA, like a matrix, only sets the order of nucleotides in the synthesized chains, and the process itself is carried out by a protein. The work of the enzyme during DNA replication is currently one of the most interesting problems. It is likely that DNA polymerase actively crawls along the double-stranded DNA molecule from one end to the other, leaving a forked reduplicated “tail” behind it. The physical principles of such work of this protein are not yet clear.

However, DNA and its individual functional regions, which carry information about the structure of proteins, do not themselves directly participate in the process of creating protein molecules. The first step towards the realization of this information recorded in the DNA strands is the so-called process of transcription, or "rewriting". In this process, on one DNA strand, as on a matrix, a chemically related polymer, ribonucleic acid (RNA), is synthesized. The RNA molecule is a single chain, the monomers of which are four kinds of ribonucleotides, which are considered as a slight modification of four kinds of DNA deoxyribonucleotides. The sequence of arrangement of four types of ribonucleotides in the resulting RNA chain exactly repeats the sequence of arrangement of the corresponding deoxyribonucleotides of one of the two DNA chains. In this way, the nucleotide sequence of genes is copied in the form of RNA molecules, i.e. the information recorded in the structure of a given gene is completely copied to RNA. A large, theoretically unlimited number of such "copies" - RNA molecules - can be removed from each gene. These molecules, rewritten in many copies as "copies" of genes and, therefore, carrying the same information as genes, disperse throughout the cell. They already directly enter into communication with the protein-synthesizing particles of the cell and take a “personal” part in the processes of creating protein molecules. In other words, they transfer information from the place where it is stored to the places where it is realized. Accordingly, these RNAs are referred to as messenger (mRNA) or messenger (mRNA).

It has been found that the mRNA chain is synthesized directly using the corresponding DNA region as a template. The synthesized mRNA chain exactly copies one of the two DNA chains in its nucleotide sequence (assuming that uracil (U) in RNA corresponds to its derivative thymine (T) in DNA). This occurs on the basis of the same structural principle of complementarity that determines DNA reduplication (Fig. 18). It turned out that when mRNA is synthesized on DNA in a cell, only one DNA strand is used as a template for the formation of an mRNA chain. Then each G of this DNA chain will correspond to C in the RNA chain under construction, each C of the DNA chain - G in the RNA chain, each T of the DNA chain - A in the RNA chain and each A of the DNA chain - Y in the RNA chain. As a result, the resulting RNA strand will be strictly complementary to the DNA template strand and, therefore, identical in nucleotide sequence (assuming T = Y) to the second DNA strand. Thus, information is “rewritten” from DNA to RNA, i.e. transcription. "Rewritten" combinations of nucleotides in the RNA chain already directly determine the arrangement of the corresponding amino acids encoded by them in the protein chain.

Here, as in the case of DNA reduplication, one of the most significant aspects of the transcription process must be its enzymatic character. DNA, which is the template in this process, entirely determines the arrangement of nucleotides in the synthesized mRNA chain, all the specificity of the resulting RNA, but the process itself is carried out by a special protein - an enzyme. This enzyme is called RNA polymerase. Its molecule has a complex organization that allows it to actively move along the DNA molecule, simultaneously synthesizing an RNA chain complementary to one of the DNA chains. The DNA molecule, which serves as a matrix, is not consumed and does not change, remaining in its original form and always ready for such rewriting from it of an unlimited number of "copies" - mRNA. The flow of these mRNAs from DNA to ribosomes constitutes the flow of information that ensures the programming of the protein-synthesizing apparatus of the cell, the totality of its ribosomes.

Thus, the considered part of the scheme describes the flow of information from DNA in the form of mRNA molecules to intracellular particles synthesizing proteins. Now we turn to a different kind of flow - to the flow of the material from which the protein must be created. The elementary units - monomers - of a protein molecule are amino acids, of which there are about 20. To create (synthesis) a protein molecule, the free amino acids present in the cell must be involved in the corresponding flow entering the protein-synthesizing particle, and already there they are arranged in a chain in a certain unique way dictated by messenger RNA. This involvement of amino acids building material to create a protein - is carried out by attaching free amino acids to special RNA molecules of a relatively small size. These RNAs, which serve to attach free amino acids to them, while not being informational, have a different - adapter - function, the meaning of which will be seen later. Amino acids are attached to one end of small chains of transfer RNA (tRNA), one amino acid per RNA molecule. For each such amino acid in the cell, there are specific adapter RNA molecules that attach only these amino acids. In such a form hung on RNA, amino acids enter the protein-synthesizing particles.

The central moment of the process of protein biosynthesis is the fusion of these two intracellular flows - the flow of information and the flow of material - in the protein-synthesizing particles of the cell. These particles are called ribosomes. Ribosomes are ultramicroscopic biochemical "machines" of molecular dimensions, where specific proteins are assembled from incoming amino acid residues, according to the plan contained in messenger RNA. Although in fig. 19 shows only one particle, each cell will contain thousands of ribsomes. The number of ribosomes determines the overall intensity of protein synthesis in the cell. The diameter of one ribosomal particle is about 20 nm. In its own way chemical nature ribosome - ribonucleoprotein: it consists of a special ribosomal RNA (this is the third class of RNA known to us in addition to information and adapter RNA) and structural ribosomal protein molecules. Together, this combination of several dozen macromolecules forms an ideally organized and reliable “machine” that has the ability to read the information contained in the mRNA chain and realize it in the form of a finished protein molecule of a specific structure. Since the essence of the process is that the linear arrangement of 20 different amino acids in the protein chain is uniquely determined by the arrangement of four different nucleotides in the chain of a chemically completely different polymer - nucleic acid (mRNA), this process, which occurs in the ribosome, is commonly referred to as "translation", or "translation" - translation, as it were, from the four-letter alphabet of nucleic acid chains to the twenty-letter alphabet of protein (polypeptide) chains. As you can see, all three are involved in the translation process. famous class RNA: messenger RNA, which is the object of translation; ribosomal RNA, which plays the role of the organizer of the protein-synthesizing ribonucleoprotein particle - the ribosome; and adapter RNAs that perform the function of a translator.

Rice. 19. Scheme of a functioning ribosome

The process of protein synthesis begins with the formation of amino acid compounds with adapter RNA molecules, or tRNAs. In this case, first, the energy “activation” of the amino acid occurs due to its enzymatic reaction with the adenosine triphosphate (ATP) molecule, and then the “activated” amino acid is connected to the end of a relatively short tRNA chain, while the increment in the chemical energy of the activated amino acid is stored in the form of energy chemical bond between amino acids and tRNA.

At the same time, the second task is solved. The fact is that the reaction between the amino acid and the tRNA molecule is carried out by an enzyme referred to as aminoacyl-tRNA synthetase. Each of the 20 amino acids has its own special enzymes that carry out the reaction with the participation of only this amino acid. Thus, there are at least 20 enzymes (aminoacyl-tRNA synthetase), each of which is specific for one particular amino acid. Each of these enzymes can react not with any tRNA molecule, but only with those that carry a strictly defined combination of nucleotides in their chain. Thus, due to the existence of a set of such specific enzymes that distinguish, on the one hand, the nature of the amino acid and, on the other hand, the nucleotide sequence of tRNA, each of the 20 amino acids is “assigned” only to certain tRNAs with a given characteristic nucleotide combination.

Schematically, some moments of the process of protein biosynthesis, as far as we present them today, are given in Fig. 19. Here, first of all, it is seen that the messenger RNA molecule is connected to the ribosome, or, as they say, the ribosome is “programmed” by the messenger RNA. At any given moment, only a relatively short segment of the mRNA chain is located directly in the ribosome itself. But it is this segment, with the participation of the ribosome, that can interact with adapter RNA molecules. Here again the principle of complementarity plays a major role.

This is the explanation of the mechanism why a given triplet of the mRNA chain corresponds to a strictly defined amino acid. An adapter RNA (tRNA) is a necessary intermediate link, or adapter, when each amino acid "recognizes" its triplet on mRNA.

On fig. Figure 19 shows that in addition to the tRNA molecule with the attached amino acid, there is one more tRNA molecule in the ribosome. But, unlike the tRNA molecule discussed above, this tRNA molecule is attached with its end to the end of the protein (polypeptide) chain that is in the process of synthesis. This position reflects the dynamics of events occurring in the ribosome during the synthesis of a protein molecule. This dynamic can be imagined as follows. Let's start with some intermediate point, shown in Fig. 19 and is characterized by the presence of a protein chain that has already begun to be built, a tRNA attached to it and that has just entered the ribosome and associated with a triplet of a new tRNA molecule with its corresponding amino acid. Apparently, the very act of attaching a tRNA molecule to an mRNA triplet located in a given place of the ribosome leads to such a mutual orientation and close contact between the amino acid residue and the protein chain under construction that covalent bond. The connection occurs in such a way that the end of the protein chain under construction (attached to tRNA in Fig. 19) is transferred from this tRNA to the amino acid residue of the incoming aminoacyl-tRNA. As a result, the "right" tRNA, having played the role of a "donor", will be free, and protein chain- transferred to the "acceptor", i.e. on the "left" (incoming) aminoacyl-tRNA. As a result, the protein chain will be extended by one amino acid and attached to the "left" tRNA. This is followed by the transfer of the “left” tRNA, together with the triplet of mRNA nucleotides associated with it, to the right, then the former “donor” tRNA molecule will be displaced from here and leave the ribosomes. In its place, a new tRNA will appear with a protein chain under construction, extended by one amino acid residue, and the mRNA chain will be advanced one triplet to the right relative to the ribosome. As a result of moving the mRNA chain one triplet to the right, the next vacant triplet (UUU) will appear in the ribosome, and the corresponding tRNA with an amino acid (phenylalanyl-tRNA) will immediately join it according to the complementary principle. This will again cause the formation of a covalent (peptide) bond between the protein chain under construction and the phenylalanine residue, and after this, the mRNA chain will move one triplet to the right with all the ensuing consequences, etc. In this way, sequentially, triplet by triplet, the chain of informational RNA is pulled through the ribosome, as a result of which the mRNA chain is “read” by the ribosome as a whole, from beginning to end. Simultaneously and in conjunction with this, a sequential, amino acid by amino acid, buildup of the protein chain occurs. Accordingly, tRNA molecules with amino acids enter the ribosome one after another and tRNA molecules without amino acids exit. Finding themselves in a solution outside the ribosome, free tRNA molecules again combine with amino acids and again carry them into the ribosome, themselves, thus, cyclically circulating without destruction and change.

Information contained in biological sequences

Biopolymers are (biological) polymers synthesized by living beings. DNA, RNA and proteins are linear polymers, that is, each monomer they contain combines with at least two other monomers. The sequence of monomers encodes information, the transmission rules of which are described by the central dogma. Information is transmitted with high precision, deterministically, and one biopolymer is used as a template for assembling another polymer with a sequence that is completely determined by the sequence of the first polymer.

Universal ways of transferring biological information

In living organisms, there are three types of heterogeneous, that is, consisting of different polymer monomers - DNA, RNA and protein. The transfer of information between them can be carried out in 3 × 3 = 9 ways. The central dogma divides these 9 types of information transfer into three groups:

  • General - found in most living organisms;
  • Special - found as an exception, in viruses and in mobile elements of the genome or in the conditions of a biological experiment;
  • Unknown - not found.

DNA replication (DNA → DNA)

DNA is the main way information is transmitted between generations of living organisms, so the exact duplication (replication) of DNA is very important. Replication is carried out by a complex of proteins that unwind the chromatin, then the double helix. After that, DNA polymerase and its associated proteins build an identical copy on each of the two strands.

Transcription (DNA → RNA)

Transcription is a biological process, as a result of which the information contained in a DNA segment is copied onto a synthesized mRNA molecule. Transcription is carried out by transcription factors and RNA polymerase. In a eukaryotic cell, the primary transcript (pre-mRNA) is often edited. This process is called splicing.

Schematic diagram of the realization of genetic information in pro- and eukaryotes.
PROKARYOTES. In prokaryotes, protein synthesis by the ribosome (translation) is not spatially separated from transcription and can occur even before the completion of mRNA synthesis by RNA polymerase. Prokaryotic mRNAs are often polycistronic, meaning they contain several independent genes.
EUKARYOTES. eukaryotic mRNA is synthesized as a precursor, pre-mRNA, which then undergoes complex staged maturation - processing, including the attachment of a cap structure to the 5 "end of the molecule, the attachment of several tens of adenine residues to its 3" end (polyadenylation), the cleavage of insignificant sections - introns and the connection with each other of significant sections - exons (splicing). In this case, the connection of exons of the same pre-mRNA can take place different ways, leading to the formation of different mature mRNAs, and ultimately different protein variants (alternative splicing). Only successfully processed mRNA is exported from the nucleus to the cytoplasm and involved in translation.

Translation (RNA → protein)

RNA replication (RNA → RNA)

RNA replication - copying an RNA chain to its complementary RNA chain using the enzyme RNA-dependent RNA polymerase. Viruses containing single-stranded (for example, picornaviruses, which include foot-and-mouth disease virus) or double-stranded RNA replicate in a similar way.

Direct translation of a protein on a DNA template (DNA → protein)

Live translation has been demonstrated in E. coli cell extracts, which contained ribosomes but no mRNA. Such extracts synthesized proteins from DNA introduced into the system, and the antibiotic neomycin enhanced this effect.

Epigenetic changes

Epigenetic changes are changes in the expression of genes that are not caused by changes in genetic information (mutations). Epigenetic changes occur as a result of modification of the level of gene expression, that is, their transcription and/or translation. The most studied type of epigenetic regulation is DNA methylation with the help of DNA methyltransferase proteins, which leads to a temporary, life-dependent inactivation of the methylated gene. However, since the primary structure of the DNA molecule does not change, this exception cannot be considered a true example of the transfer of information from protein to DNA.

prions

Prions are proteins that exist in two forms. One of the forms (conformations) of the protein is functional, usually soluble in water. The second form forms water-insoluble aggregates, often in the form of molecular polymer tubes. A monomer - a protein molecule - in this conformation is able to combine with other similar protein molecules, converting them into a second, prion-like, conformation. In fungi, such molecules can be inherited. But, as in the case of DNA methylation, the primary structure of the protein in this case remains the same, and there is no transfer of information to nucleic acids.

The history of the term "dogma"

original text(English)

My mind was, that a dogma was an idea for which there was no reasonable evidence. You see?!" And Crick gave a roar of delight. "I just didn't know what dogma meant. And I could just as well have called it the "Central Hypothesis," or - you know. Which is what I meant to say dogma was just a catch phrase

In addition, in his autobiographical book What a Mad Pursuit, Crick wrote about the choice of the word "dogma" and the problems that choice caused:

“I called this idea central dogma, I suspect, for two reasons. I have already used the word hypothesis in the sequence hypothesis, besides, I wanted to suggest that this new assumption is more central and stronger ... As it turns out, using the term dogma caused more trouble than it was worth ... Many years later, Jacques Monod told me that apparently I did not understand what is meant by the word dogma, which means a part of the faith that is not subject to doubt. I was vaguely apprehensive about this meaning of the word, but since I believed that all religious beliefs had no basis, I used the word as I understood it, and not most other people, applying it to the grandiose hypothesis that, despite the confidence it inspired, was based on a small amount of direct experimental data.

original text(English)

I called this idea the central dogma, for two reasons, I suspect. I had already used the obvious word hypothesis in the sequence hypothesis, and in addition I wanted to suggest that this new assumption was more central and more powerful. ... As it turned out, the use of the word dogma caused almost more trouble than it was worth.... Many years later Jacques Monod pointed out to me that I did not appear to underst and the correct use of the word dogma, which is a belief that cannot be doubted. I did apprehend this in a vague sort of way but since I thought that all religious beliefs were without foundation, I used the word the way I myself thought about it, not as most of the world does, and simply applied it to a grand hypothesis that, however plausible, had little direct experimental support.

see also

Notes

Links

  1. B. J. McCarthy, J. J. Holland. Denatured DNA as a Direct Template for in vitro Protein Synthesis // PNAS. - 1965. - T. 54. - S. 880-886.
  2. Werner, E. Genome Semantics, In Silico Multicellular Systems and the Central Dogma // FEBS Letters. - 2005. - V. 579. - S. 1779-1782. PMID 15763551
  3. Horace Freeland Judson. Chapter 6: My mind was, that a dogma was an idea for which there was no reasonable evidence. You see?! // The Eighth Day of Creation: Makers of the Revolution in Biology (25th anniversary edition). - 1996.

Central dogma of molecular biology

The structure of the cell nucleus

Fractionation of cells. Today, fractionation makes it possible to obtain almost any cell organelles and structures: nuclei, nucleoli, chromatin, nuclear membranes, plasma membrane, vacuoles of the endoplasmic reticulum, etc.

Special Methods

Before obtaining cell fractions, the cells are destroyed by homogenization. Further, fractions are isolated from the homogenates. Separating centrifugation is the main method for isolating cellular structures. It is based on the fact that heavier particles settle to the bottom of the centrifuge tube faster.

At low accelerations (1-3 thousand g), nuclei and intact cells settle earlier, at 15-30 thousand g, larger particles or macrosomes, consisting of mitochondria, small plastids, peroxisomes, lysosomes, etc., settle, at 50 thousand g, microsomes, fragments of the vacuolar system of the cell, settle. When re-centrifuging the mixed sub-fractions, pure fractions are isolated. For finer separation of fractions, sucrose density gradient centrifugation is used. Obtaining individual cellular components makes it possible to study their biochemistry and functional features, to create cell-free systems, for example, for ribosomes that can synthesize protein according to the messenger RNA specified by the experimenter, or for recreating cellular supramolecular structures.
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Such artificial systems help to study the subtle processes occurring in the cell.

Method cell engineering. After special treatment, various living cells can fuse with each other and form a binuclear cell or heterokaryon. Heterokaryons, especially those formed from closely related cells (for example, mice and hamsters), can enter mitosis and give rise to true hybrid cells. Other techniques make it possible to construct cells from nuclei and cytoplasm of different origins.

Today, cell engineering is widely used not only in experimental biology, but also in biotechnology. For example, when obtaining monoclonal antibodies.

The cell has a huge number of diverse functions, the main working mechanisms for performing these functions are proteins or their complexes with other biological macromolecules. Almost all processes of synthesis, decay, rearrangement of various proteins, nucleic acids, lipids, carbohydrates occur with the participation of enzyme proteins. Contraction, which leads to cell mobility or to the movement of substances and structures inside cells, is also carried out by special contractile proteins. Many cell reactions in response to external factors (viruses, hormones, foreign proteins, etc.) begin with the interaction of these factors with special cellular receptor proteins.

Proteins are the main components of almost all cellular structures.
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The structure of each individual protein is strictly specific, which is expressed in the specificity of their primary structure - in the sequence of amino acids along the polypeptide, protein chain. Such correctness in reproducing an unambiguous sequence of amino acids in a protein chain is determined by the DNA structure of that gene region, which is ultimately responsible for the structure and synthesis of this protein. This position is the main postulate of molecular biology or its ʼʼdogmaʼʼ. In addition, the central dogma emphasizes the unidirectional transmission of information: only from DNA to protein (DNA ® mRNA ® protein) and denies the return paths - from protein to nucleic acid.

Based on current knowledge, protein biosynthesis is the following schematic diagram.

the main role in determining the specific structure of proteins belongs to DNA. The DNA molecule, consisting of two intertwisted polymer chains, is a linear structure, the monomers of which are four types of deoxyribonucleotides, the alternation or sequence of which along the chain is unique and specific for each DNA molecule and each of its sections. A specific region of the DNA molecule is responsible for the synthesis of each protein. A section of a DNA molecule that contains all the information about the structure of one corresponding protein. called a cistron. Today, the concept of cistron is considered as equivalent to the concept of gene.

It is known that, unlike other components of the protein-synthesizing apparatus, the location of the DNA of eukaryotic organisms in cells is the cell nucleus. In lower (prokaryotic) organisms that do not have a well-formed cell nucleus, DNA is also separated from the rest of the protoplasm in the form of one or more compact nucleotides.

At the root of the macromolecular structure of DNA lies the so-called principle of complementarity. It means that the opposite nucleotides of two intertwisted DNA strands complement each other with their spatial structure. Such complementary - complementary - nucleotide pairs are the A-T pair (adenine-thymine) and the G-C pair (guanine-cytosine).

Synthesis of new DNA molecules in the cell occurs only on the basis of existing DNA molecules. In this case, the two chains of the original DNA molecule begin to diverge from one of the ends, and on each of the separated single-stranded sections, the second chain begins to assemble from the free nucleotides present in the medium in strict accordance with the principle of complementarity. In each "daughter" DNA molecule, one strand is entirely derived from the original, and the other is newly synthesized.

It must be emphasized that the potential for exact reproduction is inherent in the double-stranded complementary structure of DNA itself, and the discovery of this is one of the main achievements of biology.

To carry out the process of synthesis - DNA reproduction according to the scheme described above, the activity of a special enzyme called DNA polymerase is necessary. It is this enzyme that sequentially proceeds from one end of the DNA molecule to the other, the process of separating two strands with simultaneous polymerization of free nucleotides on them according to the complementary principle.

Consequently, DNA, like a matrix, only sets the order of nucleotides in the synthesized chains, and the process itself is carried out by a protein. DNA and its individual functional regions, which carry information about the structure of proteins, do not themselves directly participate in the process of creating protein molecules. The first step towards the realization of this information is the so-called transcription process, or ʼʼrewritingʼʼ. In this process, a chemically related polymer, ribonucleic acid (RNA), is synthesized on the DNA chain, as on a matrix. The RNA molecule is a single chain, the monomers of which are four types of ribonucleotides. The sequence of arrangement of four types of ribonucleotides in the resulting RNA chain exactly repeats the sequence of arrangement of the corresponding deoxyribonucleotides of one of the two DNA chains. Due to this, the information recorded in the structure of this gene is completely copied to RNA. A theoretically unlimited number of ʼʼcopiesʼʼ - RNA molecules - can be removed from each gene. RNA molecules enter into communication with protein-synthesizing particles of the cell and are directly involved in the synthesis of protein molecules. In other words, they transfer information from the places of its storage to the places of its implementation. That is why these RNAs are referred to as messenger or messenger RNAs, abbreviated as mRNA or mRNA.

The synthesized messenger RNA chain directly uses the corresponding DNA region as a template. In this case, the synthesized mRNA chain accurately copies one of the two DNA chains in its nucleotide sequence (uracil (U) in RNA corresponds to its derivative thymine (T) in DNA). Everything happens on the basis of the same principle of complementarity that determines DNA reduplication. As a result, ʼʼrewritingʼʼ or transcription of information from DNA to RNA occurs. ʼʼRewrittenʼʼ combinations of RNA nucleotides already directly determine the arrangement of the amino acids encoded by them in the protein chain.

Now how is protein made? It is known that the types of monomers of a protein molecule are amino acids, of which there are 20 different varieties. For each type of amino acid in the cell, there are specific adapter RNA molecules that attach only this type of amino acid. In the form visited on RNA, amino acids enter the protein-synthesizing particles - ribosomes, and already there, under the dictation of messenger RNA, they are placed in the chain of the synthesized protein.

The main thing in protein biosynthesis is the fusion of two intracellular flows in ribosomes - the flow of information and the flow of material. Ribosomes are biochemical "machines" of molecular dimensions, in which specific proteins are assembled from the incoming amino acid residues, according to the plan contained in the messenger RNA. Each cell contains thousands of ribsomes, the intensity of protein synthesis is determined by their number in the cell. By its chemical nature, the ribosome belongs to ribonucleoproteins and consists of a special ribosomal RNA and ribosomal protein molecules. Ribosomes have the ability to read the information contained in the mRNA chain and implement it in the form of a finished protein molecule. The essence of the process lies in the fact that the linear arrangement of 20 types of amino acids in a protein chain is determined by the arrangement of four types of nucleotides in the chain of a completely different polymer - nucleic acid (mRNA). For this reason, this process occurring in the ribosome is commonly referred to as ʼʼtranslationʼʼ, or ʼʼtranslationʼʼ - translation from the 4-letter alphabet of nucleic acid chains to the 20-letter alphabet of protein (polypeptide) chains. All three known classes of RNA are involved in this translation process: messenger RNA, which is the object of translation, ribosomal RNA, which plays the role of the organizer of the ribosome, and adapter RNA, which acts as a translator.

The process of protein synthesis begins with the formation of amino acid compounds with adapter RNA molecules. In this case, first, the energy ʼʼactivationʼʼ of the amino acid occurs due to its enzymatic reaction with the adenosine triphosphate (ATP) molecule, and then the ʼʼactivatedʼʼ amino acid is connected to the end of a relatively short tRNA chain, while the increment of the chemical energy of the activated amino acid is stored in the form of the energy of the chemical bond between the amino acid and tRNA.

It should be added that the reaction between the amino acid and the tRNA molecule is carried out by the enzyme aminoacyl-tRNA synthetase. Each of the 20 amino acids has its own enzymes that carry out the reaction with the participation of only this amino acid.

The central dogma of molecular biology is the concept and types. Classification and features of the category "Central dogma of molecular biology" 2017, 2018.

The main figure of matrix biosynthesis is nucleic acids RNA and DNA. They are polymeric molecules, which include five types of nitrogenous bases, two types of pentoses and phosphoric acid residues. Nitrogenous bases in nucleic acids can be purine (adenine, guanine) and pyrimidine (cytosine, uracil (only in RNA), thymine (only in DNA)). Depending on the structure of the carbohydrate, ribonucleic acids - contain ribose (RNA), and deoxyribonucleic acids- contain deoxyribose (DNA).

The term " matrix biosyntheses "means the ability of a cell to synthesize polymeric molecules, such as nucleic acids And squirrels, based on the template - matrix . This provides an accurate transfer of the most complex structure from existing molecules to newly synthesized ones.

Basic postulate of molecular biology

In the vast majority of cases, transmission hereditary information from the mother cell to the daughter cell is carried out using DNA (replication). For the use of genetic information by the cell itself, RNA is needed, which is formed on the DNA template (transcription). Further, RNA is directly involved in all stages of the synthesis of protein molecules ( translation) that provide the structure and activity of the cell.

Based on the above central dogma of molecular biology, according to which the transfer of genetic information is carried out only from nucleic acids (DNA and RNA). The recipient of information can be another nucleic acid (DNA or RNA) and a protein.

Central dogma of molecular biology - a rule generalizing the implementation of genetic information observed in nature: information is transmitted from nucleic acids to a protein, but not in the opposite direction. The rule was formulated by Francis Crick in 1958 and brought into line with the data accumulated by that time in 1970. The transfer of genetic information from DNA to RNA and from RNA to protein is universal for all cellular organisms without exception, and underlies the biosynthesis of macromolecules. Genome replication corresponds to the DNA → DNA informational transition. In nature, there are also transitions RNA → RNA and RNA → DNA (for example, in some viruses), as well as a change in the conformation of proteins transmitted from molecule to molecule. Transcription and translation. Conventionally, the entire process of transcription and translation can be displayed in the following diagram: Transcription is the process of reproducing information stored in DNA in the form of a single-stranded molecule and RNA (messenger RNA that transfers information about the protein structure from the cell nucleus to the cell cytoplasm to ribosomes). This process manifests itself in the synthesis of the molecule and RNA from the DNA template. A molecule and RNA consists of nucleotides, each of which includes a phosphoric acid residue, a sugar, a ribose, and one of four nitrogenous bases(A, G, C and U-uracil instead of T-tulin). Synthesis and RNA is based on the principle of complementarity, i.e. against A in one strand of DNA is Y in and RNA, and against G in DNA - C in and RNA (see Fig. Transcription - on the previous page), thus, RNA is a complementary copy of DNA or a certain section of it, and contains information encoding an amino acid or protein. Each amino acid in DNA and RNA is encoded by a sequence of 3 nucleotides, i.e. - a triplet, which is called a codon. If in transcription the recognition of two molecules by each other manifests itself only in the principle of complementarity, then in translation, in addition to complementarity (a temporary combination of a codon and RNA and an anticodon of RNA (transport RNA, which brings the amino acids necessary for protein synthesis to the place of synthesis - ribosome - see Fig. Transcription) molecular recognition manifests itself in the process of attaching an amino acid to tRNA using the enzyme codase.The fact is that the tRNA molecule consists of a head, which includes an anti-AOK triplet, consisting of a sequence of three nucleotides, and a tail having a certain how many types of tRNA anticosons exist, so many forms of tails exist, and each anticoson has its own tail shape in tRNA.How many forms of tails exist, so many types of forms of the enzyme codase, which attaches amino acids to the tail, and the shape of each codase fits only the shape Thus, tRNA carries information with it not only in the n sequence of nucleotides in the anticozone, but also in the form of a tail of the molecule. And the main transfer of information here is to reproduce the sequence of amino acids in the protein, which prompts the enzyme encoding the protein and RNA

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