Department of Oncology, Weatherall Institute of Molecular Medicine,University of Oxford, John Radcliffe Hospital, Oxford, UK.
Cell Cycle. 2011 Dec 1;10(23):3999-4008. doi: 10.4161/cc.10.23.18385.
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.
DNA 链间交联（ICLs）通过阻断包括复制和转录在内的重要细胞过程，对基因组和细胞完整性构成重大威胁。在哺乳动物细胞中，大部分 ICL 修复发生在 S 期与 DNA 复制相关联的过程中，即在复制叉因 ICL 损伤而停滞之后。在这里，我们回顾了最近的工作，表明 XPF-ERCC1 内切酶和 hSNM1A 外切酶与 SLX4 一起作用于同一途径，启动 ICL 修复，在不存在 XPF-SNM1A-SLX4 依赖性途径的情况下，MUS81-EME1 叉切开活性变得重要。另一种核酸酶，即范可尼贫血相关核酸酶（FAN1），最近也被牵连到 ICL 的修复中，我们讨论了在 ICL 停滞的复制叉处不同核酸酶的活性可能协调的方式。关于这一点，我们简要推测了含有 XPF 和 MUS81 相互作用结构域的 SLX4 在 ICL 修复核酸酶协调中的可能作用。
