Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair
Orchestrating the nucleases involved in DNA interstrand cross-link (ICL) repair
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DOI：
10.4161/cc.10.23.18385
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发表时间：
2011-12-01
期刊：
影响因子：
4.3
通讯作者：
McHugh, Peter J.
中科院分区：
文献类型：
--
作者：
Sengerova, Blanka;Wang, Anderson T.;McHugh, Peter J.
DNA链间交联（ICL）通过阻断基本的细胞过程（包括复制和转录）对基因组和细胞的完整性构成重大威胁。在哺乳动物细胞中，许多ICL修复发生在与DNA复制相关的S期，随后在ICL损伤引起的阻断处的复制叉停滞。在这里，我们回顾了最近的工作表明，XPF-ERCC 1核酸内切酶和hSNM 1A核酸外切酶在相同的途径中起作用，与SLX 4一起启动ICL修复，在缺乏XPF-SNM 1A-SLX 4依赖性途径的情况下，MUS 81-EME 1叉切割活性变得重要。另一种核酸酶，范可尼贫血相关的核酸酶（FAN 1），最近被牵连在ICLs的修复，我们讨论了可能的方式，其中不同的核酸酶在ICL停滞复制叉的活动可能是协调的。在这方面，我们简要地推测SLX 4，其中包含XPF和MUS 81相互作用的结构域，在协调ICL修复核酸酶的可能作用。
DNA interstrand cross-links (ICLs) pose a significant threat to genomic and cellular integrity by blocking essential cellular processes, including replication and transcription. In mammalian cells, much ICL repair occurs in association with DNA replication during S phase, following the stalling of a replication fork at the block caused by an ICL lesion. Here, we review recent work showing that the XPF-ERCC1 endonuclease and the hSNM1A exonuclease act in the same pathway, together with SLX4, to initiate ICL repair, with the MUS81-EME1 fork incision activity becoming important in the absence of the XPF-SNM1A-SLX4-dependent pathway. Another nuclease, the Fanconi anemia-associated nuclease (FAN1), has recently been implicated in the repair of ICLs, and we discuss the possible ways in which the activities of different nucleases at the ICL-stalled replication fork may be coordinated. In relation to this, we briefly speculate on the possible role of SLX4, which contains XPF and MUS81-interacting domains, in the coordination of ICL repair nucleases.