Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching.

Rif1 prevents resection of DNA breaks and promotes immunoglobulin class switching.
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DOI:
10.1126/science.1230624
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发表时间:
2013-02-08
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Nussenzweig MC
Nussenzweig MC
中科院分区:
其他
文献类型:
--
作者:
Di Virgilio M;Callen E;Yamane A;Zhang W;Jankovic M;Gitlin AD;Feldhahn N;Resch W;Oliveira TY;Chait BT;Nussenzweig A;Casellas R;Robbiani DF;Nussenzweig MC

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DNA双链断裂(DSBs)对基因组构成威胁,因为它们会导致遗传信息的丢失和染色体重排。DNA修复蛋白p53结合蛋白1 (53BP1)通过一种需要磷酸化的机制来限制dsb的核分解加工,从而保护基因组,但它是否直接起作用尚不清楚。在这里,我们确定了rapl相互作用因子1 (Rif1)是53BP1磷酸化依赖的共济失调-毛细血管扩张突变(ATM)相互作用因子,并表明Rif1的缺失导致小鼠5 ' -3 ' DNA末端切除。与增强的DNA切除一致,Rif1缺陷损害细胞周期G1和S期的DNA修复,干扰B淋巴细胞的类开关重组(CSR),并导致染色体dsb的积累。
DNA double-strand breaks (DSBs) represent a threat to the genome because they can lead to loss of genetic information and chromosome rearrangements. The DNA repair protein p53 binding protein 1 (53BP1) protects the genome by limiting nucleolytic processing of DSBs by a mechanism that requires its phosphorylation, but whether it does so directly is not known. Here we identify Rapl-interacting factor 1 (Rif1) as an Ataxia-Telangiectasia Mutated (ATM) phosphorylation-dependent interactor of 53BP1, and show that absence of Rif1 results in 5′-3′ DNA end resection in mice. Consistent with enhanced DNA resection, Rif1 deficiency impairs DNA repair in the G1 and S phases of the cell cycle, interferes with class switch recombination (CSR) in B lymphocytes, and leads to accumulation of chromosome DSBs.
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