hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex.
hSSB1 rapidly binds at the sites of DNA double-strand breaks and is required for the efficient recruitment of the MRN complex.
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DOI：
10.1093/nar/gkq1098
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发表时间：
2011-03
影响因子：
14.9
通讯作者：
Khanna KK
中科院分区：
文献类型：
--
作者：
Richard DJ;Savage K;Bolderson E;Cubeddu L;So S;Ghita M;Chen DJ;White MF;Richard K;Prise KM;Schettino G;Khanna KK
HSSB1是新近发现的一种单链DNA(SsDNA)结合蛋白，对ATM中高效的DNA双链断裂信号起着至关重要的作用。然而，hSSB1发挥作用以实现有效信令的机制尚不清楚。在这里，我们发现hSSB1被迅速招募到所有间期细胞(G1、S和G2)的双链DNA断裂(DSB)位置，而不依赖于CTIP、MDC1和MRN复合体(RAD50、Mre11、NBS1)。然而，从DSB位点扩增hSSB1需要MRN的功能。值得注意的是，hSSB1的沉默阻止了病灶的形成和MRN到DSB部位的募集，并导致DSB切除的后续缺陷，如RPA和单链DNA生成缺陷所明显的。我们的数据表明，hSSB1在MRN的上游发挥作用，促进其在DSB的招募，并是有效切除DSB所必需的。这些发现和以前的工作一起确定了hSSB1在控制ATM激活和活性以及随后的DSB切除和同源重组(HR)中的重要作用。
hSSB1 is a newly discovered single-stranded DNA (ssDNA)-binding protein that is essential for efficient DNA double-strand break signalling through ATM. However, the mechanism by which hSSB1 functions to allow efficient signalling is unknown. Here, we show that hSSB1 is recruited rapidly to sites of double-strand DNA breaks (DSBs) in all interphase cells (G1, S and G2) independently of, CtIP, MDC1 and the MRN complex (Rad50, Mre11, NBS1). However expansion of hSSB1 from the DSB site requires the function of MRN. Strikingly, silencing of hSSB1 prevents foci formation as well as recruitment of MRN to sites of DSBs and leads to a subsequent defect in resection of DSBs as evident by defective RPA and ssDNA generation. Our data suggests that hSSB1 functions upstream of MRN to promote its recruitment at DSBs and is required for efficient resection of DSBs. These findings, together with previous work establish essential roles of hSSB1 in controlling ATM activation and activity, and subsequent DSB resection and homologous recombination (HR).
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影响因子：
8
作者：
Saintigny, Y.;Delacote, F.;Lopez, B. S.
通讯作者：
Lopez, B. S.
影响因子：
7.7
作者：
Tomimatsu, Nozomi;Mukherjee, Bipasha;Burma, Sandeep
通讯作者：
Burma, Sandeep
影响因子：
2
作者：
Prise KM;Schettino G;Vojnovic B;Belyakov O;Shao C
通讯作者：
Shao C
DOI：
10.1073/pnas.96.5.1921
发表时间：
1999-03-02
影响因子：
11.1
作者：
Raderschall, E;Golub, EI;Haaf, T
通讯作者：
Haaf, T
影响因子：
14.9
作者：
Wadsworth, RIM;White, MF
通讯作者：
White, MF