Yeast DNA polymerase zeta (ζ) is essential for error-free replication past thymine glycol
Yeast DNA polymerase zeta (ζ) is essential for error-free replication past thymine glycol
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DOI：
10.1101/gad.1048303
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发表时间：
2003-01-01
影响因子：
10.5
通讯作者：
Prakash, L
中科院分区：
文献类型：
--
作者：
Johnson, RE;Yu, SL;Prakash, L
DNA聚合酶zeta（Pole）促进真核生物中DNA损伤的诱变旁路。酿酒酵母的遗传研究表明，相对于其他途径的贡献，Polzeta对病变旁路的贡献很小。然而，有趣的是，编码Polzeta催化亚基的REV3基因的破坏导致小鼠早期胚胎死亡。在这里，我们提出了遗传和生物化学的证据，酵母Polzeta的要求，主要是无错误的复制过去的胸腺嘧啶乙二醇（Tg），DNA损伤形成的自由基攻击频繁。这些结果提出了这样的可能性，即在酵母中，在高等真核生物中也是如此，Polzeta对Tgs的复制旁路以及阻止复制DNA聚合酶合成的其他病变做出了重大贡献。Polzeta在病变旁路中的这种卓越作用将确保快速细胞分裂在早期胚胎发育期间持续不减，从而最大限度地减少DNA链断裂、染色体畸变和随后的凋亡反应的产生。
DNA polymerase zeta (Pole) promotes the mutagenic bypass of DNA lesions in eukaryotes. Genetic studies in Saccharomyces cerevisiae have indicated that relative to the contribution of other pathways, Polzeta makes only a modest contribution to lesion bypass. Intriguingly, however, disruption of the REV3 gene, which encodes the catalytic subunit of Polzeta causes early embryonic lethality in mice. Here, we present genetic and biochemical evidence for the requirement of yeast Polzeta for predominantly error-free replication past thymine glycol (Tg), a DNA lesion formed frequently by free radical attack. These results raise the possibility that, as in yeast, in higher eukaryotes also, Polzeta makes a major contribution to the replicative bypass of Tgs as well as other lesions that block synthesis by replicative DNA polymerases. Such a preeminent role of Polzeta in lesion bypass would ensure that rapid cell divisions continue unabated during early embryonic development, thereby minimizing the generation of DNA strand breaks, chromosome aberrations, and the ensuing apoptotic response.