人源 SNM1A 和 XPF-ERCC1 协作启动 DNA 链间交联修复。
Human SNM1A and XPF-ERCC1 collaborate to initiate DNA interstrand cross-link repair.
机构信息
Weatherall Institute of Molecular Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DS, United Kingdom.
出版信息
Genes Dev. 2011 Sep 1;25(17):1859-70. doi: 10.1101/gad.15699211.
Abstract
One of the major DNA interstrand cross-link (ICL) repair pathways in mammalian cells is coupled to replication, but the mechanistic roles of the critical factors involved remain largely elusive. Here, we show that purified human SNM1A (hSNM1A), which exhibits a 5'-3' exonuclease activity, can load from a single DNA nick and digest past an ICL on its substrate strand. hSNM1A-depleted cells are ICL-sensitive and accumulate replication-associated DNA double-strand breaks (DSBs), akin to ERCC1-depleted cells. These DSBs are Mus81-induced, indicating that replication fork cleavage by Mus81 results from the failure of the hSNM1A- and XPF-ERCC1-dependent ICL repair pathway. Our results reveal how collaboration between hSNM1A and XPF-ERCC1 is necessary to initiate ICL repair in replicating human cells.
摘要
在哺乳动物细胞中，一种主要的 DNA 链间交联 (ICL) 修复途径与复制偶联，但涉及的关键因素的作用机制仍很大程度上难以捉摸。在这里，我们表明，纯化的人 SNM1A（hSNM1A），其表现出 5'-3'外切核酸酶活性，可以从单个 DNA 缺口加载并消化其底物链上的 ICL。hSNM1A 耗尽的细胞对 ICL 敏感，并积累与复制相关的 DNA 双链断裂（DSB），类似于 ERCC1 耗尽的细胞。这些 DSB 是 Mus81 诱导的，表明复制叉切割是由于 hSNM1A 和 XPF-ERCC1 依赖性 ICL 修复途径的失败所致。我们的结果揭示了 hSNM1A 和 XPF-ERCC1 之间的协作对于启动复制人类细胞中的 ICL 修复是如何必要的。
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本文引用的文献
1
Interactions among genes controlling sensitivity to radiation (RAD) and to alkylation by nitrogen mustard (SNM) in yeast.酵母中控制辐射敏感性（RAD）和氮芥烷化作用（SNM）的基因之间的相互作用。
Curr Genet. 1982 May;5(1):33-8. doi: 10.1007/BF00445738.
2
Homology-directed Fanconi anemia pathway cross-link repair is dependent on DNA replication.同源定向的范可尼贫血通路交联修复依赖于 DNA 复制。
Nat Struct Mol Biol. 2011 Apr;18(4):500-3. doi: 10.1038/nsmb.2029. Epub 2011 Mar 20.
3
SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype.SLX4，一种结构特异性内切酶的协调蛋白，在一种新的范可尼贫血亚型中发生突变。
Nat Genet. 2011 Feb;43(2):138-41. doi: 10.1038/ng.751. Epub 2011 Jan 16.
4
Disruption of mouse Slx4, a regulator of structure-specific nucleases, phenocopies Fanconi anemia.Slx4 是结构特异性核酸酶的调节因子，其在小鼠中的缺失可导致范可尼贫血样表型。
Nat Genet. 2011 Feb;43(2):147-52. doi: 10.1038/ng.752. Epub 2011 Jan 16.
5
Mutations of the SLX4 gene in Fanconi anemia.SLX4 基因突变与范可尼贫血症。
Nat Genet. 2011 Feb;43(2):142-6. doi: 10.1038/ng.750. Epub 2011 Jan 16.
6
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J Biol Chem. 2010 Jun 18;285(25):19085-91. doi: 10.1074/jbc.M109.100032. Epub 2010 Apr 12.
7
The SNM1/Pso2 family of ICL repair nucleases: from yeast to man.SNM1/Pso2 家族的 ICL 修复核酸酶：从酵母到人。
Environ Mol Mutagen. 2010 Jul;51(6):635-45. doi: 10.1002/em.20556.
8
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DNA Repair (Amst). 2010 Apr 4;9(4):429-37. doi: 10.1016/j.dnarep.2010.01.001. Epub 2010 Feb 1.
9
Measurement of DNA interstrand crosslinking in naked DNA using gel-based methods.使用基于凝胶的方法测量裸DNA中的DNA链间交联。
Methods Mol Biol. 2010;613:283-302. doi: 10.1007/978-1-60327-418-0_18.
10
XPF-ERCC1 participates in the Fanconi anemia pathway of cross-link repair.XPF-ERCC1 参与范可尼贫血通路的交联修复。
Mol Cell Biol. 2009 Dec;29(24):6427-37. doi: 10.1128/MCB.00086-09. Epub 2009 Oct 5.
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