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CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection

Ming Zeng, Laifeng Ren, Ken'Ichi Mizuno, Konstantinos Nestoras, Haibin Wang, Zizhi Tang, Liandi Guo, Daochun Kong, Qiwen Hu, Qun He, Lilin Du, Antony M. Carr () and Cong Liu ()
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Ming Zeng: Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University
Laifeng Ren: Fenyang College of Shanxi Medical University
Ken'Ichi Mizuno: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex
Konstantinos Nestoras: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex
Haibin Wang: Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University
Zizhi Tang: Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University
Liandi Guo: Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University
Daochun Kong: National Laboratory of Protein Engineering and Plant Genetic Engineering, College of Life Sciences, Peking University
Qiwen Hu: College of Basic Medical Sciences, Third Military Medical University
Qun He: State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University
Lilin Du: National Institute of Biological Sciences, 7 Science Park Road, Zhongguancun Life Science Park
Antony M. Carr: Genome Damage and Stability Centre, School of Life Sciences, University of Sussex
Cong Liu: Key Laboratory of Birth Defects and Related Diseases of Women and Children (Ministry of Education), West China Second University Hospital, Sichuan University

Nature Communications, 2016, vol. 7, issue 1, 1-11

Abstract: Abstract 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 that load the Rad51 filament to promote strand invasion, the defining feature of HR. How the resection machinery navigates nucleosome-packaged DNA is poorly understood. Here we report that in Schizosaccharomyces pombe 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 mono-ubiquitination (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.

Date: 2016
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms11364

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DOI: 10.1038/ncomms11364

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