L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment of RNF8 and RNF168 after DNA damage.
L3MBTL2 orchestrates ubiquitin signalling by dictating the sequential recruitment of RNF8 and RNF168 after DNA damage.
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DOI：
10.1038/s41556-018-0071-x
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发表时间：
2018-04
影响因子：
21.3
通讯作者：
Lou Z
中科院分区：
文献类型：
--
作者：
Nowsheen S;Aziz K;Aziz A;Deng M;Qin B;Luo K;Jeganathan KB;Zhang H;Liu T;Yu J;Deng Y;Yuan J;Ding W;van Deursen JM;Lou Z
细胞对细胞毒性DNA双链断裂的反应是将DNA修复蛋白募集到受损部位。这种募集依赖于E3泛素连接酶如RNF8和RNF168对相邻染色质区域的泛素化。RNF8和RNF168依次募集到双链断裂。然而，目前还不清楚是什么决定了序列顺序并将RNF168招募到DNA损伤中。在这里，我们揭示了致命（3）恶性脑肿瘤样蛋白2（L3MBTL2）是RNF8和RNF168之间缺失的一环。我们发现L3MBTL2被MDC 1募集，随后被E3连接酶RNF8泛素化。泛素化的L3MBTL2反过来促进RNF168向DNA损伤的募集，并促进DNA双链断裂修复。这些结果将L3MBTL2鉴定为DNA损伤后RNF8的关键靶点，并证明了DNA损伤反应途径如何通过泛素信号转导来协调。
Cells respond to cytotoxic DNA double strand breaks by recruiting DNA repair proteins to the damaged site. This recruitment is dependent on ubiquitylation of adjacent chromatin areas by E3 ubiquitin ligases such as RNF8 and RNF168. RNF8 and RNF168 are recruited sequentially to the double strand breaks. However, it is unclear what dictates the sequential order and recruits RNF168 to the DNA lesion. Here, we reveal that Lethal(3)malignant brain tumor-like protein 2 (L3MBTL2) is the missing link between RNF8 and RNF168. We found that L3MBTL2 is recruited by MDC1 and subsequently ubiquitylated by the E3 ligase RNF8. Ubiquitylated L3MBTL2, in turn, facilitates recruitment of RNF168 to the DNA lesion and promotes DNA double strand break repair. These results identify L3MBTL2 as a key target of RNF8 following DNA damage and demonstrates how the DNA damage response pathway is orchestrated by ubiquitin signaling.
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影响因子：
4.7
作者：
Cao J;Yan Q
通讯作者：
Yan Q
影响因子：
16
作者：
Lou, ZK;Minter-Dykhouse, K;Chen, JJ
通讯作者：
Chen, JJ
MBT 重复蛋白 L3MBTL2 对组蛋白的甲基化状态特异性识别
影响因子：
14.9
作者：
Guo Y;Nady N;Qi C;Allali-Hassani A;Zhu H;Pan P;Adams-Cioaba MA;Amaya MF;Dong A;Vedadi M;Schapira M;Read RJ;Arrowsmith CH;Min J
通讯作者：
Min J
影响因子：
64.5
作者：
Penengo, L;Mapelli, M;Schneider, TR
通讯作者：
Schneider, TR
DOI：
10.1083/jcb.201102018
发表时间：
2011-08-22
期刊：
The Journal of cell biology
影响因子：
--
作者：
Hamada M;Haeger A;Jeganathan KB;van Ree JH;Malureanu L;Wälde S;Joseph J;Kehlenbach RH;van Deursen JM
通讯作者：
van Deursen JM