BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping.
BRCA2 acts as a RAD51 loader to facilitate telomere replication and capping.
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DOI：
10.1038/nsmb.1943
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发表时间：
2010-12
影响因子：
16.8
通讯作者：
中科院分区：
文献类型：
--
作者：
BRCA 2是DNA修复的同源重组（HR）途径的关键组分，在双链断裂位点充当RAD 51重组酶的装载剂。在这里，我们证明了BRCA 2与端粒在S/G2期间，促进RAD 51加载到端粒。小鼠胚胎成纤维细胞（MEFs）中有条件的Brca 2缺失和Rad 51抑制，而不是Brca 1失活，导致端粒缩短和端粒信号片段的积累，这是与复制缺陷相关的端粒脆性的标志。这表明BRCA 2介导的HR反应通过促进端粒复制而有助于端粒长度的维持，并暗示BRCA 2在未受挑战的细胞增殖期间在端粒完整性中起重要作用。缺乏Brca 2的小鼠乳腺肿瘤累积端粒功能障碍诱导的病灶。BRCA 2突变的人乳腺肿瘤的端粒比BRCA 1突变的肿瘤短，这表明在BRCA 2缺陷肿瘤中观察到的基因组不稳定性部分是由于端粒功能障碍。
BRCA2 is a key component of the homologous recombination (HR) pathway of DNA repair, acting as the loader of RAD51 recombinase at sites of double-strand breaks. Here, we demonstrate that BRCA2 associates with telomeres during S/G2 and facilitates RAD51 loading onto telomeres. Conditional Brca2 deletion and Rad51 inhibition in mouse embryonic fibroblasts (MEFs), but not Brca1 inactivation, led to telomere shortening and accumulation of fragmented telomeric signals, a hallmark of telomere fragility associated with replication defects. This suggests that BRCA2-mediated HR reactions contribute to telomere length maintenance by facilitating telomere replication and implies an essential role for BRCA2 in telomere integrity during unchallenged cell proliferation. Mouse mammary tumors lacking Brca2 accumulated telomere dysfunction-induced foci. BRCA2-mutated human breast tumors had shorter telomeres than BRCA1-mutated ones, suggesting that the genomic instability observed in BRCA2-deficient tumors is due in part to telomere dysfunction.
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影响因子：
11.4
作者：
Herrera, E;Samper, E;Blasco, MA
通讯作者：
Blasco, MA
影响因子：
30.8
作者：
Connor, F;Bertwistle, D;Ashworth, A
通讯作者：
Ashworth, A
DOI：
10.1083/jcb.200811079
发表时间：
2009-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Badie S;Liao C;Thanasoula M;Barber P;Hill MA;Tarsounas M
通讯作者：
Tarsounas M
影响因子：
30.8
作者：
Muñoz, P;Blanco, R;Blasco, MA
通讯作者：
Blasco, MA
影响因子：
5.3
作者：
Jaco, I;Mu単oz, P;Blasco, MA
通讯作者：
Blasco, MA