DNA polymerase ζ in DNA replication and repair
DNA polymerase ζ in DNA replication and repair
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DOI：
10.1093/nar/gkz705
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发表时间：
2019-09-19
影响因子：
14.9
通讯作者：
Wood, Richard D.
中科院分区：
文献类型：
--
作者：
Martin, Sara K.;Wood, Richard D.
在这里，我们调查的DNA聚合酶zeta（pol zeta）在真核生物中的各种功能。在哺乳动物细胞中，REV3L（3130个残基）是DNA聚合酶的最大催化亚基。酵母中的正磷酸亚基是Rev3p。Pol zeta还包括REV 7亚基（在酵母中由Rev7编码，在哺乳动物细胞中由MAD2L2编码）和与复制型DNA聚合酶pol δ共享的两个亚基。Pol zeta用于应对酵母和哺乳动物细胞中阻止DNA复制叉的情况。最好的检查情况是translesion合成在网站的共价DNA病变，如紫外线辐射诱导的光产物。我们还强调了最近的证据，揭示了pol zeta的各种作用，超越translesion合成。例如，当复制体操作次优或在难以复制的DNA序列时，也采用pol zeta。Pol zeta还通过微同源介导的断裂诱导的复制参与修复。在酵母中可以耐受rev3缺失，但Rev3l破坏导致小鼠胚胎死亡。哺乳动物Rev3l的失活导致基因组不稳定性并引起细胞死亡和衰老程序。靶向pol zeta功能可能是癌症治疗中有用的策略，但必须考虑与pol zeta缺陷相关的染色体不稳定性。
Here, we survey the diverse functions of DNA polymerase zeta (pol zeta) in eukaryotes. In mammalian cells, REV3L (3130 residues) is the largest catalytic subunit of the DNA polymerases. The orthologous subunit in yeast is Rev3p. Pol zeta also includes REV7 subunits (encoded by Rev7 in yeast and MAD2L2 in mammalian cells) and two subunits shared with the replicative DNA polymerase, pol delta. Pol zeta is used in response to circumstances that stall DNA replication forks in both yeast and mammalian cells. The best-examined situation is translesion synthesis at sites of covalent DNA lesions such as UV radiation-induced photoproducts. We also highlight recent evidence that uncovers various roles of pol zeta that extend beyond translesion synthesis. For instance, pol zeta is also employed when the replisome operates sub-optimally or at difficult-to-replicate DNA sequences. Pol zeta also participates in repair by microhomology mediated break-induced replication. A rev3 deletion is tolerated in yeast but Rev3l disruption results in embryonic lethality in mice. Inactivation of mammalian Rev3l results in genomic instability and invokes cell death and senescence programs. Targeting of pol zeta function may be a useful strategy in cancer therapy, although chromosomal instability associated with pol zeta deficiency must be considered.