Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p
Mutagenesis in eukaryotes dependent on DNA polymerase zeta and Rev1p
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DOI：
10.1098/rstb.2000.0001
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发表时间：
2001-01-29
影响因子：
6.3
通讯作者：
Maher, VM
中科院分区：
文献类型：
--
作者：
Lawrence, CW;Maher, VM
DNA聚合酶zeta（Pol zeta）和Rev1p在芽殖酵母（Saccharomyces cerevisiae）中进行translesion复制，并共同负责该生物体中由DNA损伤诱导的几乎所有碱基对取代和移码突变。此外，Pol zeta负责酵母中的大多数自发突变，并且已被提议为负责体细胞超变的酶。Pol zeta是一种缺乏3'至5'核酸外切酶校正活性的非进行性酶，由催化亚基Rev3p和由REV7编码的第二亚基组成。与其作用一致，通过Pol zeta的延伸相对耐受引物末端的异常DNA结构，并且比酵母DNA聚合酶α（Pol α）更能够从末端错配延伸。Rev1p是一种双功能酶，具有脱氧胞苷酰转移酶活性，其在模板中掺入脱氧胞苷酰相对脱碱基位点，以及目前定义不清的第二种活性，其是绕过各种病变以及脱碱基位点所需的。酵母REV 1和REV 3的人类同源物已经被鉴定，并且基于产生针对这些基因中的一个或另一个的反义RNA的细胞的表型，它们的产物似乎也被用于翻译复制和自发诱变。我们认为Pol zeta最好被视为一种复制酶，尽管它只是间歇性地使用，但它促进了分叉处的延伸，而分叉的进展因任何原因而受阻，无论是存在未编辑的末端错配还是未修复的DNA损伤。
DNA polymerase zeta (Pol zeta) and Rev1p carry out translesion replication in budding yeast, Saccharomyces cerevisiae, and are jointly responsible for almost all base pair substitution and frameshift mutations induced by DNA damage in this organism. In addition, Pol zeta is responsible for the majority of spontaneous mutations in yeast and has been proposed as the enzyme responsible for somatic hypermutability. Pol zeta, a non-processive enzyme that lacks a 3' to 5' exonuclease proofreading activity, is composed of Rev3p, the catalytic subunit, and a second subunit encoded by REV7. In keeping with its role, extension by Pol zeta is relatively tolerant of abnormal DNA structure at the primer terminus and is much more capable of extension from terminal mismatches than yeast DNA polymerase alpha (Pol alpha). Rev1p is a bifunctional enzyme that possesses a deoxycytidyl transferase activity that incorporates deoxycytidyl opposite abasic sites in the template and a second, at present poorly defined, activity that is required for the bypass of a variety of lesions as well as abasic sites. Human homologues of the yeast REV1 and REV3 have been identified and, based on the phenotype of cells producing antisense RNA to one or other of these genes, their products appear also to be employed in translation replication and spontaneous mutagenesis. We suggest that Pol zeta is best regarded as a replication enzyme, albeit one that is used only intermittently, that promotes extension at forks the progress of which is blocked for any reason, whether the presence of an unedited terminal mismatch or unrepaired DNA lesion.