The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end resection.
The yeast Fun30 and human SMARCAD1 chromatin remodellers promote DNA end resection.
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DOI：
10.1038/nature11353
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发表时间：
2012-09-27
期刊：
影响因子：
64.8
通讯作者：
Llorente, Bertrand
中科院分区：
文献类型：
--
作者：
Costelloe, Thomas;Louge, Raphael;Tomimatsu, Nozomi;Mukherjee, Bipasha;Martini, Emmanuelle;Khadaroo, Basheer;Dubois, Kenny;Wiegant, Wouter W.;Thierry, Agnes;Burma, Sandeep;van Attikum, Haico;Llorente, Bertrand
一些同源依赖性途径可以修复潜在的致命DNA双链断裂（DSB）。所有同源重组反应共同的第一步是DSB末端的5′-3′降解，产生加载检查点和重组蛋白所需的3′单链DNA（ssDNA）。Mre 11-Rad 50-Xrs 2/NBS 1复合物和Sae 2/CtIP启动末端切除，而长距离切除依赖于核酸外切酶Exo 1或解旋酶-拓扑异构酶复合物Sgs 1-Top3-Rmi 1与核酸内切酶Dna 2。DSB发生在染色质的背景下，但切除机制如何通过核小体DNA导航是一个不太清楚的过程。在这里，我们表明，酵母S。酿酒酵母Fun 30蛋白及其人类对应物SMARCAD 1，Snf 2 ATP酶家族的两种特征不佳的ATP依赖性染色质重塑物，是直接参与DSB反应的新因子。Fun 30与DSB末端物理结合，并通过涉及其ATP酶活性的机制直接促进依赖于Exo 1和Sgs 1的末端切除。Fun 30在切除中的功能促进了喜树碱（CPT）诱导的DNA损伤的修复，当Exo 1异位过表达时，它变得不必要。有趣的是，SMARCAD 1也被募集到DSB，募集的动力学与Exo 1相似。SMARCAD 1的缺失损害末端切除、重组DNA修复，并使细胞对CPT或PARP抑制剂治疗引起的DNA损伤过敏。这些发现揭示了Fun 30和SMARCAD 1染色质重塑在染色质背景下控制末端切除、同源重组和基因组稳定性的进化保守作用。
Several homology-dependent pathways can repair potentially lethal DNA double-strand breaks (DSBs). The first step common to all homologous recombination reactions is the 5′-3′ degradation of DSB ends that yields 3′ single-stranded DNA (ssDNA) required for loading of checkpoint and recombination proteins. The Mre11-Rad50-Xrs2/NBS1 complex and Sae2/CtIP initiate end resection while long-range resection depends on the exonuclease Exo1 or the helicase-topoisomerase complex Sgs1-Top3-Rmi1 with the endonuclease Dna2. DSBs occur in the context of chromatin, but how the resection machinery navigates through nucleosomal DNA is a process that is not well understood. Here, we show that the yeast S. cerevisiae Fun30 protein and its human counterpart SMARCAD1, two poorly characterized ATP-dependent chromatin remodelers of the Snf2 ATPase family, are novel factors that are directly involved in the DSB response. Fun30 physically associates with DSB ends and directly promotes both Exo1- and Sgs1-dependent end resection through a mechanism involving its ATPase activity. The function of Fun30 in resection facilitates repair of camptothecin (CPT)-induced DNA lesions, and it becomes dispensable when Exo1 is ectopically overexpressed. Interestingly, SMARCAD1 is also recruited to DSBs and the kinetics of recruitment is similar to that of Exo1. Loss of SMARCAD1 impairs end resection, recombinational DNA repair and renders cells hypersensitive to DNA damage resulting from CPT or PARP inhibitor treatments. These findings unveil an evolutionarily conserved role for the Fun30 and SMARCAD1 chromatin remodelers in controlling end resection, homologous recombination and genome stability in the context of chromatin.
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DOI：
10.1083/jcb.200510130
发表时间：
2006-04-24
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bekker-Jensen S;Lukas C;Kitagawa R;Melander F;Kastan MB;Bartek J;Lukas J
通讯作者：
Lukas J
影响因子：
16
作者：
Beli, Petra;Lukashchuk, Natalia;Wagner, Sebastian A.;Weinert, Brian T.;Olsen, Jesper V.;Baskcomb, Linda;Mann, Matthias;Jackson, Stephen P.;Choudhary, Chunaram
通讯作者：
Choudhary, Chunaram
Snf2 同源物 Fun30 充当同型二聚体 ATP 依赖性染色质重塑酶。
DOI：
10.1074/jbc.m109.082149
发表时间：
2010-03-26
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Awad S;Ryan D;Prochasson P;Owen-Hughes T;Hassan AH
通讯作者：
Hassan AH
影响因子：
16.8
作者：
通讯作者：
--
影响因子：
3.3
作者：
Pardo, B;Ma, E;Marcand, S
通讯作者：
Marcand, S