Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete
Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete
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DOI：
10.1073/pnas.0812578106
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发表时间：
2009-01-27
影响因子：
11.1
通讯作者：
Haber, James E.
中科院分区：
文献类型：
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作者：
Kim, Jung-Ae;Haber, James E.
响应于DNA双链断裂（DSB），染色质被损伤依赖性检查点激酶快速修饰。此外，染色质的解体发生在断裂位点。损伤诱导的染色质结构改变参与了检查点的维持。然而，尚未确定当DSB修复完成时染色质如何恢复到未受损状态。在这里，我们显示了两个染色质组装因子（CAFs），Asf 1和CAF-1，在关闭芽殖酵母中的DNA损伤检查点的参与。DSB修复或γ-H2 AX的形成不依赖于CAF-1蛋白、Cac 1或Asf 1。这些蛋白质的缺乏不会损害细胞在未修复的DSB（适应）存在下恢复细胞周期进程的能力。然而，从细胞周期检查点停滞的恢复时，DSB是修复基因转换是基本上有缺陷的CAF-1和Asf 1的情况下，而删除CAC 1或ASF 1单独几乎没有影响。我们认为CAF-1和Asf 1的功能冗余，通过恢复染色质结构的DSB修复完成后，使检查点失活。
In response to a DNA double-strand break (DSB), chromatin is rapidly modified by the damage dependent checkpoint kinases. Also, disassembly of chromatin occurs at the break site. The damage-induced modification of chromatin structure is involved in the maintenance of the checkpoint. However, it has not been determined how chromatin is restored to its undamaged state when DSB repair is complete. Here, we show the involvement of two chromatin assembly factors (CAFs), Asf1 and CAF-1, in turning off the DNA damage checkpoint in budding yeast. DSB repair or formation of gamma-H2AX does not depend on either the CAF-1 protein, Cac1, or Asf1. Absence of these proteins does not impair the ability of cells to resume cell cycle progression in the presence of an unrepaired DSB (adaptation). However, recovery from cell cycle checkpoint arrest when the DSB is repaired by gene conversion is substantially defective in the absence of both CAF-1 and Asf1, whereas deleting CAC1 or ASF1 individually had little effect. We suggest that CAF-1 and Asf1 function redundantly to deactivate the checkpoint by restoring chromatin structure on the completion of DSB repair.