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An OB-fold complex controls the repair pathways for DNA double-strand breaks.

Nature communications (2018-09-27)
Shengxian Gao, Sumin Feng, Shaokai Ning, Jingyan Liu, Huayu Zhao, Yixi Xu, Jinfeng Shang, Kejiao Li, Qing Li, Rong Guo, Dongyi Xu
ZUSAMMENFASSUNG

53BP1 with its downstream proteins, RIF1, PTIP and REV7, antagonizes BRCA1-dependent homologous recombination (HR) and promotes non-homologous end joining (NHEJ) in an unclear manner. Here we show that REV7 forms a complex with two proteins, FAM35A and C20ORF196. We demonstrate that FAM35A preferentially binds single-strand DNA (ssDNA) in vitro, and is recruited to DSBs as a complex with C20ORF196 and REV7 downstream of RIF1 in vivo. Epistasis analysis shows that both proteins act in the same pathway as RIF1 in NHEJ. The defects in HR pathway to repair DSBs and the reduction in resection of broken DNA ends in BRCA1-mutant cells can be largely suppressed by inactivating FAM35A or C20ORF196, indicating that FAM35A and C20ORF196 prevent end resection in these cells. Together, our data identified a REV7-FAM35A-C20ORF196 complex that binds and protects broken DNA ends to promote the NHEJ pathway for DSB repair.

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Sigma-Aldrich
Monoklonaler ANTI-FLAG® M2-Antikörper in Maus hergestellte Antikörper, clone M2, purified immunoglobulin (Purified IgG1 subclass), buffered aqueous solution (10 mM sodium phosphate, 150 mM NaCl, pH 7.4, containing 0.02% sodium azide)
Sigma-Aldrich
Anti-C20orf196 antibody produced in rabbit, Prestige Antibodies® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution
Sigma-Aldrich
MISSION® esiRNA, targeting human FAM35A