A genome-wide screen identifies p97 as an essential regulator of DNA damage-dependent CDT1 destruction.
A genome-wide screen identifies p97 as an essential regulator of DNA damage-dependent CDT1 destruction.
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DOI：
10.1016/j.molcel.2011.06.036
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发表时间：
2011-10-07
期刊：
影响因子：
16
通讯作者：
Harper JW
中科院分区：
文献类型：
--
作者：
Raman M;Havens CG;Walter JC;Harper JW
包括复制许可因子CDT 1和组蛋白甲基转移酶SET 8在内的几种蛋白质在DNA复制和修复过程中被E3泛素连接酶CRL 4CDT 2靶向蛋白水解。CRL 4CDT 2的功能与复制和修复相关联，因为它仅泛素化与染色质结合的PCNA相关的底物。在这里，我们报告了一个全基因组siRNA筛选，确定了紫外线照射后CDT 1破坏所需的多种因素。其中，核苷酸切除修复因子促进CDT 1破坏，这是由于其在将PCNA募集到受损DNA中的作用。C 0 P9/信号体通过CUL 4去螺旋化调节CDT 2稳定性。最后，p97 AAA+-ATP酶和它的辅因子UFD 1所需的蛋白酶体依赖性的去除泛素化的CDT 1和SET 8从染色质和随后的降解在体内和在非洲爪蟾卵提取物系统在体外。这项研究提供了深入了解，并为进一步探索，促进及时降解的染色质相关的CRL 4CDT 2底物的途径的资源。
Several proteins including the replication licensing factor CDT1 and the histone methyltransferase SET8 are targeted for proteolysis during DNA replication and repair by the E3 ubiquitin ligase CRL4CDT2. CRL4CDT2 function is coupled to replication and repair because it only ubiquitinates substrates that associate with chromatin-bound PCNA. Here, we report a genome-wide siRNA screen that identifies multiple factors necessary for CDT1 destruction after UV irradiation. Among these, nucleotide excision repair factors promote CDT1 destruction due to a role in recruiting PCNA to damaged DNA. The COP9/Signalosome regulates CDT2 stability through CUL4 deneddylation. Finally, the p97 AAA+-ATPase and its cofactor UFD1 are required for proteasome-dependent removal of ubiquitinated CDT1 and SET8 from chromatin and their subsequent degradation both in vivo and in a Xenopus egg extract system in vitro. This study provides insight into, and a resource for the further exploration of, pathways that promote timely degradation of chromatin-associated CRL4CDT2 substrates.
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影响因子：
--
作者：
Cope GA;Deshaies RJ
通讯作者：
Deshaies RJ
影响因子：
16
作者：
Heo JM;Livnat-Levanon N;Taylor EB;Jones KT;Dephoure N;Ring J;Xie J;Brodsky JL;Madeo F;Gygi SP;Ashrafi K;Glickman MH;Rutter J
通讯作者：
Rutter J
DOI：
10.1083/jcb.200403106
发表时间：
2004-05-24
期刊：
The Journal of cell biology
影响因子：
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作者：
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通讯作者：
Helin K
影响因子：
64.5
作者：
Koegl, M;Hoppe, T;Jentsch, S
通讯作者：
Jentsch, S
影响因子：
16
作者：
Abbas T;Shibata E;Park J;Jha S;Karnani N;Dutta A
通讯作者：
Dutta A