Sgs1 helicase is required for efficient PCNA monoubiquitination and translesion DNA synthesis in Saccharomyces cerevisiae
Sgs1 helicase is required for efficient PCNA monoubiquitination and translesion DNA synthesis in Saccharomyces cerevisiae
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Sgs1 解旋酶是酿酒酵母中有效 PCNA 单泛素化和跨损伤 DNA 合成所必需的
DOI：
10.1007/s00294-017-0753-0
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发表时间：
2018-04
期刊：
影响因子：
2.5
通讯作者：
Xiao Wei
中科院分区：
文献类型：
--
作者：
Li Fangfang;Ball Lindsay G;Fan Li;Hanna Michelle;Xiao Wei
DNA损伤耐受（DDT）是真核生物用来处理模板链上的复制障碍，并分为两个平行的途径，通过在Lys 164残基上的增殖细胞核抗原（PCNA）的顺序泛素化激活。Rad 6-Rad 18介导的PCNA单泛素化促进跨损伤DNA合成（TLS），并且单泛素化的PCNA可以通过Mms 2-Ubc 13-Rad 5复合物进一步多泛素化，导致无错误的损伤旁路。我们以前报道过，DNA解旋酶Sgs 1是无差错病变旁路所需的，可能是通过双霍利迪连接迁移和随后的决议。令人惊讶的是，使用rev 1和rev 3作为诱饵的合成基因阵列（SGA）筛选没有显示出预期的sgs 1合成效应，表明sgs 1可能参与TLS。在这里，我们报告了详细的遗传分析，表明Sgs 1在有效的TLS中起着关键作用，并且可能是导致PCNA单倍泛素化的DNA损伤信号所必需的。这些研究共同说明，Sgs 1参与DDT的两个分支，并可能在途径选择中发挥作用。
DNA-damage tolerance (DDT) is employed by eukaryotes to deal with replication blocks on the template strand, and is divided into two parallel pathways that are activated by sequential ubiquitination of proliferating cell nuclear antigen (PCNA) at the Lys164 residue. Rad6-Rad18-mediated PCNA monoubiquitination promotes translesion DNA synthesis (TLS) and the monoubiquitinated PCNA can be further polyubiquitinated by an Mms2-Ubc13-Rad5 complex, leading to error-free lesion bypass. We previously reported that the DNA helicase Sgs1 is required for error-free lesion bypass, probably through the double-Holliday junction migration and subsequent resolution. Surprisingly, a synthetic genetic array (SGA) screen using rev1 and rev3 as baits did not reveal an anticipated synthetic effect with sgs1, indicating a possible involvement of Sgs1 in TLS. Here, we report detailed genetic analyses demonstrating that Sgs1 plays a key role in efficient TLS and that it is probably required for the signaling of DNA damage leading to PCNA monoubiquitination. These studies collectively illustrate that Sgs1 participates in both branches of DDT and possibly plays a role in pathway choice.
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