Neddylation inhibits CtIP-mediated resection and regulates DNA double strand break repair pathway choice

被引:44
|
作者
Jimeno, Sonia [1 ,2 ]
Jesus Fernandez-Avila, Maria [1 ]
Cruz-Garcia, Andres [1 ,2 ]
Cepeda-Garcia, Cristina [1 ]
Gomez-Cabello, Daniel [1 ]
Huertas, Pablo [1 ,2 ]
机构
[1] Ctr Andaluz Biol Mol & Med Regenerat CABIMER, Seville 41092, Spain
[2] Univ Seville, Dept Genet, E-41080 Seville, Spain
基金
欧洲研究理事会;
关键词
DAMAGE RESPONSE; HOMOLOGOUS RECOMBINATION; NEDD8-ACTIVATING ENZYME; END RESECTION; UBIQUITIN; REVEALS; BRCA1; SAE2; ATM;
D O I
10.1093/nar/gku1384
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
DNA double strand breaks are the most cytotoxic lesions that can occur on the DNA. They can be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as a major controller of repair pathway choice. Neddylation inhibition changes the normal repair profile toward an increase on homologous recombination. Indeed, RNF111/UBE2M-mediated neddylation acts as an inhibitor of BRCA1 and CtIP-mediated DNA end resection, a key process in repair pathway choice. By controlling the length of ssDNA produced during DNA resection, protein neddylation not only affects the choice between NHEJ and homologous recombination but also controls the balance between different recombination subpathways. Thus, protein neddylation status has a great impact in the way cells respond to DNA breaks.
引用
收藏
页码:987 / 999
页数:13
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