The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells
The ACF1 Complex Is Required for DNA Double-Strand Break Repair in Human Cells
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DOI：
10.1016/j.molcel.2010.12.003
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发表时间：
2010-12-22
期刊：
影响因子：
16
通讯作者：
Yasui, Akira
中科院分区：
文献类型：
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作者：
Lan, Li;Ui, Ayako;Yasui, Akira
DNA双链断裂（DSB）通过非同源末端连接（NHEJ）或同源重组（HR）修复，但细胞修复过程仍然难以捉摸。我们在这里表明，ATP依赖性染色质重塑因子，ACF 1和SNF 2 H，在DSB快速积累，并需要在人体细胞中的DSB修复。如果ACF 1或SNF 2 H的表达受到抑制，细胞对X射线和化学处理变得非常敏感，产生DSB，DSB仍然无法修复。ACF 1直接与KU 70相互作用，是KU蛋白在DSB积累所必需的。在产生DSB的处理后，KU 70/80复合物在物理上变得与CHRAC复合物的染色质重塑因子（包括ACF 1、SNF 2 H、CHRAC 15和CHRAC 17）更相关。此外，NHEJ的频率以及由染色体DNA中的DSB诱导的HR在这些因子中的任一个耗尽的细胞中显著降低。因此，ACF 1及其复合物在DSB修复中发挥重要作用。
DNA double-strand breaks (DSBs) are repaired via nonhomologous end-joining (NHEJ) or homologous recombination (HR), but cellular repair processes remain elusive. We show here that the ATP-dependent chromatin-remodeling factors, ACF1 and SNF2H, accumulate rapidly at DSBs and are required for DSB repair in human cells. If the expression of ACF1 or SNF2H is suppressed, cells become extremely sensitive to X-rays and chemical treatments producing DSBs, and DSBs remain unrepaired. ACF1 interacts directly with KU70 and is required for the accumulation of KU proteins at DSBs. The KU70/80 complex becomes physically more associated with the chromatin-remodeling factors of the CHRAC complex, which includes ACF1, SNF2H, CHRAC15, and CHRAC17, after treatments producing DSBs. Furthermore, the frequency of NHEJ as well as HR induced by DSBs in chromosomal DNA is significantly decreased in cells depleted of either of these factors. Thus, ACF1 and its complexes play important roles in DSBs repair.