POLYMERASES

From Big Medical Encyclopedia

POLYMERASES — nukleotidiltransferaza (KF 2.7.7...), the enzymes of a class of transferases catalyzing synthesis of nucleic acids (RNA or DNA) from ribo-or deoxyribonucleotides. Depending on type of the connection which is formed as a result of reaction, P. divide into DNA polymerases (dezoksiribonukleozidtrifosfat: полидезоксирибонуклеотид-нуклеотидилтрансферазы) and RNA polymerases (ribonukleozidtrifosfat: polyribonucleotide-nukleotidiltransferazy). Synthesis of N ukleinovy acids (see) it can be carried out in the matrix and not matrix way. Reactions of matrix synthesis nucleinic to - the t proceeding with P.'s participation are the cornerstone of such vital processes as replication (see) and transcription (see). DNA polymerases are responsible also for a reparation («curing») of damages deoxyribonucleic acid (see), edges occurs by cutting the damaged site and recovery of the correct sequence of nucleotides. The items catalyzing matrix synthesis use an odnotyazhevy piece of a polynucleotide chain as a matrix. The polynucleotide with the sequence of nitrogen bases, the complementary sequence of nitrogen bases of a nucleinic to-you-matrix, i.e. the molecule representing as if a chemical negative of a matrix is as a result formed. Further with use of this «negative» the copy of a matrix can be synthesized.

The reactions catalyzed by matrix polymerases can be presented the following equation:

where (NMF)P — the growing polynucleotide chain from n of links (DNA or RNA); NTF — ribo-or dezo-ksiribonukleozidtrifosfat, FFN — an inorganic pyrophosphate; Me 2+ — ions of bivalent metal (Mg 2+ or Mn 2+ ). As a result of nucleophilic attack of alpha atom of phosphorus of a nukleozidtrifosfat Z '-the hydroxylic group located on the end of the growing chain forms phosphodiester communication. The synthesizable chain grows in the direction 5' - >Z'; accession of the following nucleotide is selective: it results from pairing with the nitrogen base which is a part of a matrix chain complementary to it the bases of the next nukleozidtrifosfat.

Except matrix P., in an organism the enzymes catalyzing not matrix synthesis nucleinic to - t are found. One of such enzymes — a polinukleotidfosforilaz (KF 2.7.7.8) — catalyzes synthesis RNA (see) from ribonukleoziddifosfat, and the sequence of their inclusion is any and submits only to statistical regularities. Reaction is reversible, at fiziol, conditions enzyme catalyzes a phosphorolysis nucleinic to - you; synthesis of a polynucleotide happens only at high concentration of substrate. Along with ekzonukleaza (see. Nucleases ) these enzymes carry to depolymerases, in a cell they take part in disintegration of molecules nucleinic to - t. Not matrix synthesis nucleinic to - t catalyze also terminal nukleotidil-transferases providing building of nucleotides on 3' - the end of a polynucleotide chain. By means of such enzymes completion of a trailer acceptor trinucleotide in acceptor RNA, and also an extension polyadenylate-nogo of a trailer fragment to information RNA is carried out (it facilitates transport of RNA from a kernel in cytoplasm).

P.'s studying began in the mid-fifties 20 century. In 1955 Mr. of Gryunberg-Manago (M. of Grunberg-Manago) and S. Ochoa reported about allocation of a polinukleotidfosforilaza, in A. Kornberg's laboratory in the same time the DNA polymerase from Escherichia coli was received. In 1960 — 1961 the RNA polymerase was received, and in 1970 Baltimore (D. Baltimore) and H. Temin reported about discovery of the enzyme providing synthesis of DNA on a polynucleotide matrix of RNA which received the name the return transcriptase — revertaza (see).

DNA polymerases meet in all live organisms. Depending on type of a matrix distinguish DNA-dependent DNA polymerases (replikaza) and RNA-dependent DNA polymerases (the return transcriptases, or revertaza). DNA-dependent DNA polymerases from Escherichia coli are most in details investigated. In this object three similar enzymes with similar properties are revealed: DNA polymerases of I, II and III. One of them — the DNA polymerase of III, showing the maximum activity, has complex subunit structure and participates in replication of a genome. DNA polymerases of I and II differ from this enzyme on quarternary structure (they are monomers) and function (they provide a reparation of a genome though it is not excluded that the DNA polymerase of I participates also in replication).

In zooblasts three DNA-dependent types of DNA polymerases are also revealed: alpha, beta and scale. From them alpha enzyme has more complex structure, than a beta DNA polymerase. Both enzymes are localized preferential in a kernel; attribute to an alpha DNA polymerase replicative function; beta enzyme provides a reparation of a genome; and gamma enzyme carries out DNA replication in mitochondrions.

The RNA-dependent DNA polymerase is allocated from the RNA-containing viruses, its presence at cells of nek-ry animals needs confirmation.

RNA polymerases are found in all live organisms: on a matrix of dvukhtyazhevy DNA by means of DNA-dependent RNA polymerases RNA of animal and plant cells, bacteria and DNA-containing of viruses are synthesized. At the RNA-containing viruses on a matrix one - or dvukhtyazhevy RNA by means of RNA-dependent RNA polymerases their so-called remarks are formed.

Believe that the RNA polymerase from Escherichia coli consists at least of 5 subunits: two alpha chains about a pier. it is powerful apprx. 40 000, one beta chains (a pier. weight 155 000), one beta '-chains (a pier. weight 165 000) and one σ-chain (pier. weight 12 000 — 16 000). Also so-called σ-particle is necessary for normal functioning of this enzyme (a pier. weight 95 000), providing linkng of enzyme with promoter of matrix DNA. In cells of eukaryotes three forms of a RNA polymerase are found: nucleolar, mitochondrial and enzyme from nucleohyaloplasm.

Quantitative definition of activity of P. is carried out, measuring inclusion in a polynucleotide chain of a mononucleotide, marked by radioisotope (most often 14 C).

Success achieved in a research P. allowed to move ahead in studying of nek-ry malignant tumors. For diagnosis of leukoses the biochemical test is used: the size of activity of the return transcriptase in erythrocytes. Receiving an antiserum against the return transcriptase of viruses, and also the directed search and synthesis of specific inhibitors of this enzyme allow to hope for creation effective chemical and biol, methods of controlling with leukoses and nek-ry others onkol, diseases. The enzymes participating in exchange nucleinic to - t, including and P., use for synthesis of the genes coding some important polypeptides in medical practice: interferon, Somatotropinum, somatostatin, etc. (see. Genetic engineering ).



Bibliography: To Gauza G. G. Inhibitors of biosynthesis of DNA, in book: Molek. biol., under the editorship of A. A. Nichiporovich, t. 16, page 93, M., 1979; Debov S. S. and Tikhon of the Tax Code about T. I. Biosynthesis and artificial synthesis of nucleic acids, Vestn. USSR Academy of Medical Sciences, No. 8, page 11, 1979; Davidson J. Biochemistry of nucleic acids, the lane with English, M., 1976; Kiselyov L. L. RNA — the directed synthesis of DNA, in book: Molek. biol., under the editorship of A. A. Nichiporovich, t. 11, M., 1978; Kornberg A. Synthesis of DNA, the lane with English, M., 1977; Prangishvili D. A. and Bibilashvili R. Sh. Enzymes of not matrix synthesis of poliri-bonukleotid, in book: Usp. biol, chemical, under the editorship of B. N. Stepanenko, t. 20, page 5, M., 1979.


O. D. Lopina.

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