Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans.
Regulated proteolysis of DNA polymerase eta during the DNA-damage response in C. elegans.
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DOI：
10.1016/j.molcel.2008.11.016
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发表时间：
2008-12-26
期刊：
影响因子：
16
通讯作者：
Michael, W. Matthew
中科院分区：
文献类型：
--
作者：
Kim, Seung-Hwan;Michael, W. Matthew
POLH-1 （pol eta）跨损伤合成DNA聚合酶和GEI-17 SUMO E3连接酶对于秀丽隐杆线虫胚胎中受损染色体的有效复制至关重要。在这里，我们研究了POLH-1在这些胚胎的DNA损伤反应中是如何被调节的。我们报道DNA损伤触发POLH-1的降解，并且降解是由Cul4-Ddb1-Cdt2 （CRL4-Cdt2）途径介导的，该途径先前已被证明在S期降解复制因子Cdt1。我们还发现GEI-17保护POLH-1免受CRL4-Cdt2介导的破坏，直到它在TLS中发挥其功能之后，这可能是通过POLH-1的sumo化。这些研究表明，POLH-1经历DNA损伤诱导的蛋白水解，而GEI-17调节这种蛋白水解的时间。讨论了该系统在TLS之后如何控制从复制分叉中删除POLH-1的含义。
Both the POLH-1 (pol eta) trans-lesion synthesis DNA polymerase and the GEI-17 SUMO E3 ligase are essential for the efficient replication of damaged chromosomes in C. elegans embryos. Here, we study how POLH-1 is regulated during a DNA damage response in these embryos. We report that DNA damage triggers the degradation of POLH-1, and that degradation is mediated by the Cul4-Ddb1-Cdt2 (CRL4-Cdt2) pathway that has previously been shown to degrade the replication factor Cdt1 during S phase. We also show that GEI-17 protects POLH-1 from CRL4-Cdt2 mediated destruction, until after it has performed its function in TLS, and this is likely via SUMOylation of POLH-1. These studies reveal that POLH-1 undergoes DNA damage-induced proteolysis, and that GEI-17 regulates the timing of this proteolysis. Implications for how this system may control the removal of POLH-1 from replication forks after TLS are discussed.
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影响因子：
16
作者：
Haracska, L;Kondratick, CM;Prakash, L
通讯作者：
Prakash, L
影响因子：
3.8
作者：
Lehmann, Alan R.;Niimi, Atsuko;Green, Catherine M.
通讯作者：
Green, Catherine M.
影响因子：
3.3
作者：
Jones, CA;Hartman, PS
通讯作者：
Hartman, PS
DOI：
10.1016/0921-8777(91)90050-y
发表时间：
1991-09-01
期刊：
MUTATION RESEARCH
影响因子：
--
作者：
HARTMAN, P;REDDY, J;SVENDSEN, BA
通讯作者：
SVENDSEN, BA
影响因子：
7.5
作者：
O'Connell, Brenda C.;Harper, J. Wade
通讯作者：
Harper, J. Wade