REV1 is important for the ATR-Chk1 DNA damage response pathway in Xenopus egg extracts.
REV1 is important for the ATR-Chk1 DNA damage response pathway in Xenopus egg extracts.
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DOI：
10.1016/j.bbrc.2015.03.077
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发表时间：
2015-05-08
影响因子：
3.1
通讯作者：
Yan, Shan
中科院分区：
文献类型：
--
作者：
DeStephanis, Darla;McLeod, Melissa;Yan, Shan
跨损伤DNA合成(TLS)聚合酶Rev1参与绕过不可修复的DNA损伤，如链间交联(ICLS)。然而，Rev1在DNA损伤反应(DDR)途径中的潜在作用尚未确定。在这项研究中，我们提供了证据来证明Rev1在非洲爪哇卵子提取物中对丝裂霉素C(MMC)诱导的ICL的ATR-Chk1检查点激活中起着先前未被发现但却很重要的作用。我们进一步明确了Rev1在包括ATR、ATIP、TopBP1和Rad9-Rad1-Hus1复合体在内的检查点蛋白复合体组装的下游对MMC诱导的DDR途径染色质上的ICL的作用。值得注意的是，结构域解剖分析表明，Rev1的C末端结构域，而不是单个泛素结合基序，对于Rev1与MMC损伤的染色质结合和MMC诱导的Chk1磷酸化是重要的。然而，ATR-Chk1 DDR途径似乎对于Rev1与MMC损伤的染色质的优先结合是必不可少的。综上所述，Rev1在非洲爪哇卵提取物中的DDR途径中是重要的。
The translesion DNA synthesis (TLS) polymerase REV1 is implicated in the bypass of the irreparable DNA damage such as interstrand crosslinks (ICLs). However, the potential role of REV1 in DNA damage response (DDR) pathway has not been determined. In this research communication, we provide evidence to demonstrate that REV1 plays a previously unidentified but important role in the ATR-Chk1 checkpoint activation in response to mitomycin C (MMC)-induced ICLs in Xenopus egg extracts. We further pinpointed that REV1 plays a downstream role of a checkpoint protein complex assembly including ATR, ATRIP, TopBP1 and the Rad9-Rad1-Hus1 complex to MMC-induced ICLs on chromatin in the DDR pathway. Notably, domain dissection analysis demonstrates that a C-terminal domain, but not the individual ubiquitin binding motifs, of REV1 is important for the binding of REV1 to MMC-damaged chromatin and the MMC-induced Chk1 phosphorylation. Yet, the ATR-Chk1 DDR pathway appears to be dispensable for the preferential association of REV1 to MMC-damaged chromatin. Taken together, REV1 is important for the DDR pathway in Xenopus egg extracts.
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