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CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection

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Version 2 2023-06-12, 06:38
Version 1 2023-06-09, 01:02
journal contribution
posted on 2023-06-12, 06:38 authored by Ming Zeng, Ren Laifeng, Ken'ichi Mizuno, Konstantinos Nestoras, Haibin Wang, Zizhi Tang, Liandi Guo, Daochun Kong, Qiwen Hu, Qun He, Lilin Du, Antony CarrAntony Carr, Cong Liu
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.

History

Publication status

  • Published

File Version

  • Published version

Journal

Nature Communications

ISSN

2041-1723

Publisher

Nature Publishing Group

Issue

1

Volume

7

Article number

a11364

Department affiliated with

  • Sussex Centre for Genome Damage Stability Publications

Full text available

  • Yes

Peer reviewed?

  • Yes

Legacy Posted Date

2016-04-26

First Open Access (FOA) Date

2016-04-26

First Compliant Deposit (FCD) Date

2016-04-26

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