CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection

Zeng, Ming, Laifeng, Ren, Mizuno, Ken'ichi, Nestoras, Konstantinos, Wang, Haibin, Tang, Zizhi, Guo, Liandi, Kong, Daochun, Hu, Qiwen, He, Qun, Du, Lilin, Carr, Antony M and Liu, Cong (2016) CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection. Nature Communications, 7. p. 11364. ISSN 2041-1723

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Double strand breaks repaired by homologous recombination (HR) are first resected to form single stranded DNA which binds replication protein A (RPA). RPA attracts mediators which load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Using Schizosaccharomyces pombe we report that a conserved DDB1-CUL4-associated factor (DCAF), Wdr70, is recruited to DSBs as part of the Cullin4-DDB1 ubiquitin ligase (CRL4Wdr70) and stimulates distal H2B lysine 119 monoubiquitination(uH2B). Wdr70 deletion, or uH2B loss, results in increased loading of the checkpoint adaptor and resection inhibitor Crb253BP1, decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb253BP1 loss, or when the Set9 methyltransferase that creates docking sites for Crb2 is deleted. Finally we establish that this histone regulatory cascade similarly controls DSB resection in human cells.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
Subjects: Q Science > Q Science (General)
Depositing User: Gee Wheatley
Date Deposited: 26 Apr 2016 08:08
Last Modified: 11 Mar 2017 21:54

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