Replicative polymerases (pols) cannot accommodate damaged template bases, and these pols stall when such offenses are encountered during S phase. Rather than repairing the damaged base, replication past it may proceed via one of two DNA damage tolerance (DDT) pathways, allowing replicative DNA synthesis to resume. In translesion DNA synthesis (TLS), a specialized TLS pol is recruited to catalyze stable, yet often erroneous, nucleotide incorporation opposite damaged template bases. In template switching, the newly synthesized sister strand is used as a damage-free template to synthesize past the lesion. In eukaryotes, both pathways are regulated by the conjugation of ubiquitin to the PCNA sliding clamp by distinct E2/E3 pairs. Whereas monoubiquitination by Rad6/Rad18 mediates TLS, extension of this ubiquitin to a polyubiquitin chain by Ubc13-Mms2/Rad5 routes DDT to the template switching pathway. In this review, we focus on the monoubiquitination of PCNA by Rad6/Rad18 and summarize the current knowledge of how this process is regulated.

中文翻译：

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DNA损伤耐受期间Rad6 / Rad18活性的调节。

复制型聚合酶（pols）无法容纳受损的模板碱基，并且在S期遇到此类攻击时，这些pols会停止运行。除了修复受损的碱基，还可以通过两个DNA损伤耐受（DDT）途径之一进行复制，从而使复制的DNA合成得以恢复。在跨病变的DNA合成（TLS）中，招募了专门的TLS pol，以催化与受损模板碱基相对的稳定（但通常是错误的）核苷酸掺入。在模板转换中，新合成的姊妹链被用作无损伤模板以合成通过病变。在真核生物中，这两种途径均受泛素与PCNA滑动钳的缀合（通过不同的E2 / E3对）调控。Rad6 / Rad18的单泛素化介导TLS，Ubc13-Mms2 / Rad5将该泛素延伸至多泛素链，将DDT路由至模板转换途径。在这篇综述中，我们集中于Rad6 / Rad18对PCNA的单泛素化作用，并总结了有关如何调节该过程的最新知识。