Zhestianikov V D
Institute of Cytology RAS, St. Petersburg.
Tsitologiia. 2000;42(9):837-43.
The review is devoted to mechanisms of repair gaps in DNA daughter strand, formed during the stall of moving replication forks and restart of replication in cells after the action of DNA damaging agents (predominantly--UV light). The repair of daughter DNA, or postreplication DNA repair (PRR), is realized by error-free (non-mutagenic) and error-prone (mutagenic) pathways. The former is a recombination repair, or recombination between two sister duplexes. By this way the major part of postreplication gaps is eliminated. The second way is related with the induction of SOS-response. In Escherichia coli cells mutagenic SOS-response is realized by proteins RecA, UmuD, UmuC, DNA-polymerase III holoenzyme and others. In E. coli some mutagenic enzymes--DNA-polymerase IV (the product of dinB gene) and DNA-polymerase V (the product of umuDC genes) have been recently discovered. In Saccharomyces cerevisiae cells postreplicative translesion synthesis is realized by newly discovered enzymes deoxycytidilmonophosphatetransferase (encoded by REV1 gene), DNA-polymerase zeta (encoded by REV3 gene), DNA-polymerase eta (encoded by RAD30 gene). All the three enzymes share a great homology with UmuC enzyme of E. coli. DNA polymerase eta correctly inserts adenine residues in the daughter strand opposite noncoded thymine residues in cyclobutane pyrimidine dimer. Based on RAD6 gene of S. cerevisiae, human cells hREV1, hREV3 and hRAD30A have been obtained to encode, respectively, deoxycytidiltransferase, DNA-polymerase zeta and DNA-polymerase eta. It has been shown that the defect of PRR DNA in xeroderma pigmentosum variant is associated with DNA-polymerase eta deficiency. This defect is corrected by the extract of intact HeLa cells. The importance of newly discovered enzymes in the system of mechanisms of DNA repair and replication is discussed.
本综述致力于探讨在DNA损伤剂（主要是紫外线）作用后，细胞中移动的复制叉停滞和复制重新启动期间形成的DNA子链缺口的修复机制。子代DNA的修复，即复制后DNA修复（PRR），通过无差错（非诱变）和易错（诱变）途径实现。前者是重组修复，即两条姐妹双链体之间的重组。通过这种方式，复制后缺口的大部分得以消除。第二种方式与SOS反应的诱导有关。在大肠杆菌细胞中，诱变SOS反应由RecA、UmuD、UmuC、DNA聚合酶III全酶等蛋白质实现。最近在大肠杆菌中发现了一些诱变酶——DNA聚合酶IV（dinB基因的产物）和DNA聚合酶V（umuDC基因的产物）。在酿酒酵母细胞中，复制后跨损伤合成由新发现的脱氧胞苷单磷酸转移酶（由REV1基因编码）、DNA聚合酶ζ（由REV3基因编码）、DNA聚合酶η（由RAD30基因编码）实现。这三种酶与大肠杆菌的UmuC酶具有高度同源性。DNA聚合酶η能在子代链中正确地在环丁烷嘧啶二聚体中未编码的胸腺嘧啶残基对面插入腺嘌呤残基。基于酿酒酵母的RAD6基因，已获得人类细胞hREV1、hREV3和hRAD30A，它们分别编码脱氧胞苷转移酶、DNA聚合酶ζ和DNA聚合酶η。研究表明，着色性干皮病变异型中PRR DNA的缺陷与DNA聚合酶η缺乏有关。这种缺陷可通过完整的HeLa细胞提取物得到纠正。文中讨论了新发现的酶在DNA修复和复制机制系统中的重要性。
