Delineation of the role of chromatin assembly and the Rtt101Mms1 E3 ubiquitin ligase in DNA damage checkpoint recovery in budding yeast.
Delineation of the role of chromatin assembly and the Rtt101Mms1 E3 ubiquitin ligase in DNA damage checkpoint recovery in budding yeast.
复制标题
DOI：
10.1371/journal.pone.0180556
复制
发表时间：
2017
期刊：
影响因子：
3.7
通讯作者：
Tyler JK
中科院分区：
文献类型：
--
作者：
Diao LT;Chen CC;Dennehey B;Pal S;Wang P;Shen ZJ;Deem A;Tyler JK
DNA损伤检查点在DNA双链断裂（DSB）时被激活。我们之前已经表明，由组蛋白伴侣Asf 1介导的染色质组装在DSB修复后触发酵母中DNA损伤检查点的失活，也称为检查点恢复。在这里，我们表明，染色质组装因子1（CAF-1）也有助于染色质重组后DSB修复，解释其在检查点恢复的作用。为了了解染色质组装如何促进检查点恢复，我们发现在asf 1突变体中DSB修复后持续存在损伤传感器Ddc 1和Ddc 2。编码E3泛素连接酶复合物Rtt 101 Mms 1的基因在诱导DSB后的存活中对ASF 1具有上位性，并且Rtt 101 Mms 1是DSB修复后检查点恢复所需的，但不是染色质组装所需的。相比之下，被Rtt 101 Mms 1降解的Mms 22底物适配器本身需要用于DSB修复。MMS 22的缺失阻断了Rad 51在DSB处的加载，而ASF 1或RTT 101的缺失导致Rad 51的持续加载。我们建议，检查点恢复是促进Rtt 101 Mms 1介导的Mms 22的泛素化，以停止Mms 22依赖性加载Rad 51到双链DNA DSB修复后，与染色质组装介导的位移Rad 51和检查点传感器从网站的修复。
The DNA damage checkpoint is activated in response to DNA double-strand breaks (DSBs). We had previously shown that chromatin assembly mediated by the histone chaperone Asf1 triggers inactivation of the DNA damage checkpoint in yeast after DSB repair, also called checkpoint recovery. Here we show that chromatin assembly factor 1 (CAF-1) also contributes to chromatin reassembly after DSB repair, explaining its role in checkpoint recovery. Towards understanding how chromatin assembly promotes checkpoint recovery, we find persistent presence of the damage sensors Ddc1 and Ddc2 after DSB repair in asf1 mutants. The genes encoding the E3 ubiquitin ligase complex Rtt101Mms1 are epistatic to ASF1 for survival following induction of a DSB, and Rtt101Mms1 are required for checkpoint recovery after DSB repair but not for chromatin assembly. By contrast, the Mms22 substrate adaptor that is degraded by Rtt101Mms1 is required for DSB repair per se. Deletion of MMS22 blocks loading of Rad51 at the DSB, while deletion of ASF1 or RTT101 leads to persistent Rad51 loading. We propose that checkpoint recovery is promoted by Rtt101Mms1-mediated ubiquitylation of Mms22 in order to halt Mms22-dependent loading of Rad51 onto double-stranded DNA after DSB repair, in concert with the chromatin assembly-mediated displacement of Rad51 and checkpoint sensors from the site of repair.
登录
查看更多内容
影响因子：
3.8
作者：
Clemenson, Celine;Marsolier-Kergoat, Marie-Claude
通讯作者：
Marsolier-Kergoat, Marie-Claude
影响因子：
3.8
作者：
Duro, Eris;Vaisica, Jessica A.;Rouse, John
通讯作者：
Rouse, John
DOI：
10.1073/pnas.0812578106
发表时间：
2009-01-27
影响因子：
11.1
作者：
Kim, Jung-Ae;Haber, James E.
通讯作者：
Haber, James E.
影响因子：
4.5
作者：
Ben-Aroya S;Agmon N;Yuen K;Kwok T;McManus K;Kupiec M;Hieter P
通讯作者：
Hieter P
影响因子：
14.9
作者：
Krejci L;Altmannova V;Spirek M;Zhao X
通讯作者：
Zhao X