An RNF168 fragment defective for focal accumulation at DNA damage is proficient for inhibition of homologous recombination in BRCA1 deficient cells.
An RNF168 fragment defective for focal accumulation at DNA damage is proficient for inhibition of homologous recombination in BRCA1 deficient cells.
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DOI：
10.1093/nar/gku421
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发表时间：
2014-07
影响因子：
14.9
通讯作者：
Stark JM
中科院分区：
文献类型：
--
作者：
Muñoz MC;Yanez DA;Stark JM
The E3 ubiquitin ligase RNF168 is a DNA damage response (DDR) factor that promotes monoubiquitination of H2A/H2AX at K13/15, facilitates recruitment of other DDR factors (e.g. 53BP1) to DNA damage, and inhibits homologous recombination (HR) in cells deficient in the tumor suppressor BRCA1. We have examined the domains of RNF168 important for these DDR events, including chromosomal HR that is induced by several nucleases (I-SceI, CAS9-WT and CAS9-D10A), since the inducing nuclease affects the relative frequency of distinct repair outcomes. We found that an N-terminal fragment of RNF168 (1-220/N221*) efficiently inhibits HR induced by each of these nucleases in BRCA1 depleted cells, and promotes recruitment of 53BP1 to DNA damage and H2AX monoubiquitination at K13/15. Each of these DDR events requires a charged residue in RNF168 (R57). Notably, RNF168-N221* fails to self-accumulate into ionizing radiation induced foci (IRIF). Furthermore, expression of RNF168 WT and N221* can significantly bypass the role of another E3 ubiquitin ligase, RNF8, for inhibition of HR in BRCA1 depleted cells, and for promotion of 53BP1 IRIF. We suggest that the ability for RNF168 to promote H2A/H2AX monoubiquitination and 53BP1 IRIF, but not RNF168 self-accumulation into IRIF, is important for inhibition of HR in BRCA1 deficient cells.
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DOI：
10.4161/cc.20919
发表时间：
2012-07-01
期刊：
Cell cycle (Georgetown, Tex.)
影响因子：
--
作者：
Gatti M;Pinato S;Maspero E;Soffientini P;Polo S;Penengo L
通讯作者：
Penengo L
核小体酸性贴片促进RNF168-和RING1B/BMI1依赖性H2AX以及H2A泛素化和DNA损伤信号传导。
影响因子：
4.5
作者：
Leung JW;Agarwal P;Canny MD;Gong F;Robison AD;Finkelstein IJ;Durocher D;Miller KM
通讯作者：
Miller KM
影响因子：
56.9
作者：
Jinek, Martin;Chylinski, Krzysztof;Charpentier, Emmanuelle
通讯作者：
Charpentier, Emmanuelle
影响因子：
64.5
作者：
Gudjonsson, Thorkell;Altmeyer, Matthias;Lukas, Claudia
通讯作者：
Lukas, Claudia
RAD18 传递 DNA 损伤信号以引发同源重组修复。
影响因子：
21.3
作者：
Huang, Jun;Huen, Michael S. Y.;Kim, Hongtae;Leung, Charles Chung Yun;Glover, J. N. Mark;Yu, Xiaochun;Chen, Junjie
通讯作者：
Chen, Junjie