DNA-damage tolerance (DDT) is an important mechanism for living cells to bypass replication blocks on the template strand. In Saccharomyces cerevisiae, DDT is mediated by the RAD6 epistasis group of genes, consisting of two parallel pathways: error-prone translesion DNA synthesis (TLS), and error-free lesion bypass. The two pathways are activated by sequential ubiquitination of PCNA on the Lys164 residue. When a replication fork is stalled at a lesion, PCNA is first monoubiquitinated by Rad6-Rad18, which leads to the TLS pathway. The subsequent ubiquitination by the Mms2-Ubc13-Rad5 complex on the monoubiquitinated PCNA is to form a Lys63-linked polyubiquitin chain that promotes error-free lesion bypass. While the TLS pathway has been extensively characterized, the molecular events leading to error-free lesion bypass by polyubiquitinated PCNA are largely obscure. Furthermore, PCNA can also be sumoylated at the same Lys164 residue, which helps to recruit Srs2, a helicase and anti-recombinase. This review summarizes recent advances in our understanding of error-free DDT and its interplay with Srs2 and homologous recombination.

中文翻译：

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酿酒酵母中的无错DNA损伤耐受性。

DNA损伤耐受性（DDT）是活细胞绕过模板链上复制嵌段的重要机制。在酿酒酵母中，DDT是由RAD6上位基因组介导的，该组基因由两个平行途径组成：易错的病灶DNA合成（TLS）和无错的病灶旁路。这两个途径被Lys164残基上PCNA的顺序泛素化激活。当复制叉停在病变处时，PCNA首先被Rad6-Rad18单泛素化，从而导致TLS途径。Mms2-Ubc13-Rad5复合物在单泛素化PCNA上的后续泛素化作用将形成Lys63连接的聚泛素链，从而促进无错病变旁路。TLS路径已被广泛地描述，导致多泛素化PCNA绕过无错病变的分子事件在很大程度上是模糊的。此外，PCNA还可以在相同的Lys164残基上被磺酰化，这有助于募集Srs2，解旋酶和抗重组酶。这篇综述总结了我们对无差错滴滴涕及其与Srs2和同源重组的相互作用的理解的最新进展。