Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks.
Multiple Rad5 activities mediate sister chromatid recombination to bypass DNA damage at stalled replication forks.
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DOI：
10.1016/j.molcel.2010.03.020
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发表时间：
2010-06-11
期刊：
影响因子：
16
通讯作者：
Kowalski D
中科院分区：
文献类型：
--
作者：
Minca EC;Kowalski D
阻断复制的DNA损伤被绕过，以完成染色体复制并保持细胞活力和基因组稳定性。Rad5是酵母中的一种PCNA多聚泛素连接酶和DNA依赖性ATP酶，与推定的肿瘤抑制因子直接相关，并通过未知机制控制无错误的损伤旁路。为了确定体内的机制，我们研究了Rad5的作用，并分析了在复制起点存在的位点特异性停滞叉的损伤旁路过程中形成的DNA结构。Rad5介导的重组依赖性，X形DNA结构的形成含有霍利迪姐妹染色单体之间的连接。缺少这些损伤诱导的染色单体连接的突变体在解决停滞的分叉、重新开始复制和完成染色体复制方面有缺陷。Rad5多聚泛素连接酶和ATP酶结构域都有助于复制叉重组。我们的研究结果表明，多种活动的Rad5功能协调同源重组因子，使复制模板切换事件，加入姐妹染色单体在停滞叉和绕过DNA损伤。
DNA damage that blocks replication is bypassed in order to complete chromosome duplication and preserve cell viability and genome stability. Rad5, a PCNA polyubiquitin ligase and DNA-dependent ATPase in yeast, is orthologous to putative tumor suppressors and controls error-free damage bypass by an unknown mechanism. To identify the mechanism in vivo, we investigated the roles of Rad5 and analyzed the DNA structures that form during damage bypass at site-specific stalled forks present at replication origins. Rad5 mediated the formation of recombination-dependent, X-shaped DNA structures containing Holliday junctions between sister chromatids. Mutants lacking these damage-induced chromatid junctions were defective in resolving stalled forks, restarting replication and completing chromosome duplication. Rad5 polyubiquitin ligase and ATPase domains both contributed to replication fork recombination. Our results indicate that multiple activities of Rad5 function coordinately with homologous recombination factors to enable replication template switch events that join sister chromatids at stalled forks and bypass DNA damage.
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DOI：
10.1073/pnas.0805685105
发表时间：
2008-08-26
影响因子：
11.1
作者：
Motegi, Akira;Liaw, Hung-Jiun;Myung, Kyungjae
通讯作者：
Myung, Kyungjae
影响因子：
16
作者：
Blastyák A;Pintér L;Unk I;Prakash L;Prakash S;Haracska L
通讯作者：
Haracska L
影响因子：
11.4
作者：
Neecke, H;Lucchini, G;Longhese, MP
通讯作者：
Longhese, MP
影响因子：
4.3
作者：
Haase, Steven B.;Reed, Steven I.
通讯作者：
Reed, Steven I.
影响因子：
5.3
作者：
Gangavarapu, Venkateswarlu;Prakash, Satya;Prakash, Louise
通讯作者：
Prakash, Louise