[Detailed model of semi-conservative DNA replication. Possible role of DNA-polymerase errors in fragmented copying of both matrix strands].
A model of semiconservative DNA synthesis is considered. The model is based on a suggestion that the synthesis proceeds in the course of one-directional stretching of both matrix strands through the replicase complex (replisome), or of one-directional movement of the replisome along the chromosome. Each nucleotide link of the matrix strand find itself successively in the section of RNA primer synthesis, in the section of DNA polymerase and in the control section of a proofreading 3' leads to 5' exonuclease. Deoxynucleoside incorrectly joined by DNA polymerase of the replisome to the 3'-OH end of growing chain are, as a rule, removed when transferred in the control section. Since the reverse movement is prohibited, the DNA polymerase loses the 3'-OH end of new DNA chain and proves to be incapable to continue the synthesis. It can be renewed only after a new RNA primer formation. For continuation of the DNA synthesis after an incorrect deoxynucleotide addition, replicase must take two more mistakes in succession: to retain the incorrect nucleotide and to join the next one to this unproperly arranged primer. Only in that case the non-complementary nucleotide in a new DNA chain can escape the action of proofreading exonucleases. Hence, according to the model under discussion, the frequency of mutations should be many times lower than that of incorrect nucleotide joinings. The latter results, as a rule, in DNA chain synthesis cessation and in fragments formation. Taking into consideration the frequency of spontaneous mutations in bacteria (about 10(-9) per base-pair), the frequency of non-complementary joinings during semiconservative synthesis can be suggested of the order 10(-3) in accordance with the average Okazaki fragments size of 1000 nucleotides. Another possible reason for periodical interruptions of semiconservative DNA synthesis and for fragments formation is a distortion of replisome structure, accompanying the release of the matrix strand being copied in the direction of already replicated chromosome region. Both mechanisms can participate concurrently in DNA fragments formation. If replisomes are attached to a cell membrane, the sites of chromosome that are also fastened in the membrane, in particular, the site of "origin", are to be replicated using some mobile replicase complex.
D004261:DNA Replication; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology / Q000378:metabolism; D008954:Models, Biological
D004259:DNA-Directed DNA Polymerase
Detalizirovannaia model' polukonservativnoĭ replikatsii DNK. Vozmozhaia rol' oshibok DNK-polimerazy v pofragmentnom kopirovanii obeikh matrichnykh niteĭ