Rad5 coordinates translesion DNA synthesis pathway by recognizing specific DNA structures in saccharomyces cerevisiae
Rad5 coordinates translesion DNA synthesis pathway by recognizing specific DNA structures in saccharomyces cerevisiae
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Rad5 通过识别酿酒酵母中的特定 DNA 结构来协调跨损伤 DNA 合成途径
DOI：
10.1007/s00294-018-0807-y
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发表时间：
2018-08-01
期刊：
影响因子：
2.5
通讯作者：
Fu, Yu V.
中科院分区：
文献类型：
--
作者：
Fan, Qifu;Xu, Xin;Fu, Yu V.
DNA修复对于维持基因组的完整性至关重要。除了处理特定类型DNA损伤的各种DNA修复途径外，DNA损伤耐受性（DDT）促进绕过复制叉遇到的DNA复制阻断，以防止细胞死亡。出芽酵母Rad5在DDT途径中起着至关重要的作用，其结构表明Rad5可以识别受损的DNA或停滞的复制分叉，这表明Rad5在DDT途径选择中起着重要作用。据报道，在S期，在甲基磺酸盐（MMS）存在下，Rad5形成亚核灶。通过分析MMS处理后Rad5病灶的形成，我们发现Rad5募集到受损部位需要一些特定的DNA结构，而不是增殖细胞核抗原的单泛素化。此外，碱基切除修复（BER）通路失活大大减少了Rad5焦点的形成，这表明Rad5识别由BER产生的特定DNA结构。我们还发现过表达的翻译合成聚合酶Polη在Rad5灶的形成中起负作用。基于这些数据，我们提出了一个改进的DDT通路模型，其中Rad5在激活DDT通路中发挥作用。
DNA repair is essential to maintain genome integrity. In addition to various DNA repair pathways dealing with specific types of DNA lesions, DNA damage tolerance (DDT) promotes the bypass of DNA replication blocks encountered by the replication fork to prevent cell death. Budding yeast Rad5 plays an essential role in the DDT pathway and its structure indicates that Rad5 recognizes damaged DNA or stalled replication forks, suggesting that Rad5 plays an important role in the DDT pathway choice. It has been reported that Rad5 forms subnuclear foci in the presence of methyl methanesulfonate (MMS) during the S phase. By analyzing the formation of Rad5 foci after MMS treatment, we showed that some specific DNA structures rather than mono-ubiquitination of proliferating cell nuclear antigen are required for the recruitment of Rad5 to the damaged site. Moreover, inactivation of the base excision repair (BER) pathway greatly decreased the Rad5 focus formation, suggesting that Rad5 recognizes specific DNA structures generated by BER. We also identified a negative role of overexpressed translesion synthesis polymerase Polη in the formation of Rad5 foci. Based on these data, we propose a modified DDT pathway model in which Rad5 plays a role in activating the DDT pathway.