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首页> 外文期刊>Molecular and Cellular Biology >A Role for Yeast and Human Translesion Synthesis DNA Polymerases in Promoting Replication through 3-Methyl Adenine
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A Role for Yeast and Human Translesion Synthesis DNA Polymerases in Promoting Replication through 3-Methyl Adenine

机译：酵母和人类跨病变合成DNA聚合酶在促进通过3-甲基腺嘌呤复制中的作用。

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摘要

3-Methyl adenine (3meA), a minor-groove DNA lesion, presents a strong block to synthesis by replicative DNA polymerases (Pols). To elucidate the means by which replication through this DNA lesion is mediated in eukaryotic cells, here we carry out genetic studies in the yeast Saccharomyces cerevisiae treated with the alkylating agent methyl methanesulfonate. From the studies presented here, we infer that replication through the 3meA lesion in yeast cells can be mediated by the action of three Rad6-Rad18-dependent pathways that include translesion synthesis (TLS) by Polη or -ζ and an Mms2-Ubc13-Rad5-dependent pathway which presumably operates via template switching. We also express human Pols ι and κ in yeast cells and show that they too can mediate replication through the 3meA lesion in yeast cells, indicating a high degree of evolutionary conservation of the mechanisms that control TLS in yeast and human cells. We discuss these results in the context of previous observations that have been made for the roles of Pols η, ι, and κ in promoting replication through the minor-groove N2-dG adducts.
机译：3-甲基腺嘌呤（3meA）是一种小沟槽DNA损伤，对复制DNA聚合酶（Pols）的合成具有很强的抑制作用。为了阐明通过这种DNA损伤在真核细胞中介导的复制的方法，在此我们对用烷基化剂甲磺酸甲酯处理过的酵母进行了遗传研究。从这里提出的研究中，我们推断酵母细胞中通过3meA损伤的复制可以通过三种Rad6-Rad18依赖性途径（包括Polη或-ζ的跨损伤合成（TLS）和Mms2-Ubc13-Rad5）的作用来介导。依赖的途径，大概通过模板交换来起作用。我们还在酵母细胞中表达人Polsι和κ，并显示它们也可以通过酵母细胞中的3meA损伤介导复制，这表明在酵母和人细胞中控制TLS的机制具有高度的进化保守性。我们在先前的观察中讨论了这些结果，这些观察是针对Polsη，ι和κ在通过小沟N 2 -dG加合物促进复制中的作用而进行的。

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