XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4.

XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4.
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DOI:
10.1016/j.molcel.2014.03.015
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发表时间:
2014-05-08
期刊:
影响因子:
16
通讯作者:
Knipscheer, Puck
Knipscheer, Puck
中科院分区:
生物学1区
文献类型:
--
作者:
Douwel, Daisy Klein;Boonen, Rick A. C. M.;Long, David T.;Szypowska, Anna A.;Raschle, Markus;Walter, Johannes C.;Knipscheer, Puck

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DNA链间交联(ICL)是一种以共价方式连接双螺旋的沃森链和克里克链的剧毒损伤,在高等真核生物中通过复杂的复制偶联途径进行修复。ICL修复中最早的DNA加工事件是在ICL的任一侧上切割亲本DNA(“脱钩”),这允许病变绕过。切口严重依赖于Fanconi贫血途径,其激活涉及FANCD 2蛋白的泛素化。使用非洲爪蟾卵提取物,支持复制偶联ICL修复,我们表明,3′瓣核酸内切酶XPF-ERCC 1与SLX 4/FANCP合作进行脱钩切口。XPF-ERCC 1和SLX 4向ICL的有效募集依赖于FANCD 2及其泛素化。这些数据有助于确定范可尼贫血途径促进复制偶联ICL修复中关键事件的分子机制。
DNA interstrand crosslinks (ICLs), highly toxic lesions that covalently link the Watson and Crick strands of the double helix, are repaired by a complex, replication-coupled pathway in higher eukaryotes. The earliest DNA processing event in ICL repair is the incision of parental DNA on either side of the ICL (“unhooking”), which allows lesion bypass. Incisions depend critically on the Fanconi anemia pathway, whose activation involves ubiquitylation of the FANCD2 protein. Using Xenopus egg extracts, which support replication-coupled ICL repair, we show that the 3′ flap endonuclease XPF-ERCC1 cooperates with SLX4/FANCP to carry out the unhooking incisions. Efficient recruitment of XPF-ERCC1 and SLX4 to the ICL depends on FANCD2 and its ubiquitylation. These data help define the molecular mechanism by which the Fanconi anemia pathway promotes a key event in replication-coupled ICL repair.
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