DNA damage tolerance relies on homologous recombination (HR) and translesion synthesis (TLS) mechanisms to fill in the ssDNA gaps generated during passing of the replication fork over DNA lesions in the template. Whereas TLS requires specialized polymerases able to incorporate a dNTP opposite the lesion and is error‐prone, HR uses the sister chromatid and is mostly error‐free. We report that the HR protein Rad52—but not Rad51 and Rad57—acts in concert with the TLS machinery (Rad6/Rad18‐mediated PCNA ubiquitylation and polymerases Rev1/Pol ζ) to repair MMS and UV light‐induced ssDNA gaps through a non‐recombinogenic mechanism, as inferred from the different phenotypes displayed in the absence of Rad52 and Rad54 (essential for MMS‐ and UV‐induced HR); accordingly, Rad52 is required for efficient DNA damage‐induced mutagenesis. In addition, Rad52, Rad51, and Rad57, but not Rad54, facilitate Rad6/Rad18 binding to chromatin and subsequent DNA damage‐induced PCNA ubiquitylation. Therefore, Rad52 facilitates the tolerance process not only by HR but also by TLS through Rad51/Rad57‐dependent and ‐independent processes, providing a novel role for the recombination proteins in maintaining genome integrity.

中文翻译：

---

Rad52 在 DNA 损伤耐受过程中跨损伤合成中的非重组作用


DNA 损伤耐受性依赖于同源重组 (HR) 和跨损伤合成 (TLS) 机制来填补复制叉越过模板中 DNA 损伤期间产生的 ssDNA 缺口。 TLS 需要专门的聚合酶，能够将 dNTP 与病变相对，并且容易出错，而 HR 使用姐妹染色单体，并且基本上不会出错。我们报告 HR 蛋白 Rad52（而不是 Rad51 和 Rad57）与 TLS 机制（Rad6/Rad18 介导的 PCNA 泛素化和聚合酶 Rev1/Pol z）协同作用，通过非重组机制，从缺乏 Rad52 和 Rad54 时表现出的不同表型推断出来（对于 MMS 和 UV 诱导的 HR 至关重要）；因此，Rad52 是有效的 DNA 损伤诱导诱变所必需的。此外，Rad52、Rad51 和 Rad57（但不是 Rad54）促进 Rad6/Rad18 与染色质的结合以及随后的 DNA 损伤诱导的 PCNA 泛素化。因此，Rad52 不仅通过 HR 促进耐受过程，还通过 Rad51/Rad57 依赖和独立过程促进 TLS 耐受过程，为重组蛋白在维持基因组完整性方面提供了新的作用。