ATR homolog Mec1 controls association of DNA polymerase ζ-Rev1 complex with regions near a double-strand break
ATR homolog Mec1 controls association of DNA polymerase ζ-Rev1 complex with regions near a double-strand break
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DOI：
10.1016/j.cub.2006.01.063
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发表时间：
2006-03-21
期刊：
影响因子：
9.2
通讯作者：
Sugimoto, K
中科院分区：
文献类型：
--
作者：
Hirano, Y;Sugimoto, K
DNA聚合酶zeta（Pol zeta）和Rev 1有助于绕过DNA损伤，称为跨损伤DNA合成（TLS）[1-3]。Pol zeta由两个亚基组成，一个由REV 3（催化亚基）编码，另一个由REV 7编码。Rev 1作为脱氧胞苷酰转移酶，将dCMP插入病变对面。Pol zeta和Rev 1已被证明在芽殖酵母酿酒酵母中以相同的TLS途径起作用[2，3]。在这里，我们。显示芽殖酵母Pol zeta和Rev 1形成复合物并与双链断裂（DSB）结合在一起。Rev 1作为Pol zeta-Rev 1复合物的组成部分，在与DSB的结合中起非催化作用。在芽殖酵母中，ATR同源物Mec 1在DNA损伤检查点反应中起着核心作用[4，5]。我们进一步表明，Mec 1依赖性磷酸化促进Pol zeta-Rev 1与DSB的关联。Rev 1与DSB的结合既不需要Rad 24检查点-钳加载器的功能[5]，也不需要Rad 6-Rad 18介导的PCNA泛素化[3]。我们的研究结果揭示了Mec 1在Pol zeta-Rev 1复合物定位于DNA损伤中的新作用，并突出了TLS聚合酶与检查点反应的联系。
DNA polymerase zeta (Pol zeta) and Rev1 contribute to the bypassing of DNA lesions, termed translesion DNA synthesis (TLS) [1-3]. Pol zeta consists of two subunits, one encoded by REV3 (the catalytic subunit) and the other encoded by REV7. Rev1 acts as a deoxycytidyl transferase, inserting dCMP opposite lesions. Pol zeta and Rev1 have been shown to operate in the same TLS pathway in the budding yeast Saccharomyces cerevisiae [2, 3]. Here, we. show that budding yeast Pol zeta and Rev1 form a complex and associate together with double-strand breaks (DSBs). As a component of the Pol zeta-Rev1 complex, Rev1 plays a noncatalytic role in the association with DSBs. In budding yeast, the ATR-homolog Mec1 plays a central role in the DNA-damage checkpoint response [4, 5]. We further show that Mec1-dependent phosphorylation promotes the Pol zeta-Rev1 association with DSBs. Rev1 association with DSBs requires neither the function of the Rad24 checkpoint-clamp loader [5] nor the Rad6-Rad18-mediated ubiquitination of PCNA [3]. Our results reveal a novel role of Mec1 in the localization of the Pol zeta-Rev1 complex to DNA lesions and highlight a linkage of TLS polymerases to the checkpoint response.