Homologous recombination

Histone

Gene

Cell biology

DNA-binding protein

Molecular biology

Biology

Neddylation

Schizosaccharomyces

FANCD2

Ubiquitin ligase

RAD51

Histone H2B

Ubiquitin

Replication protein A

DDB1

Genetics

Saccharomyces cerevisiae

DNA repair

Transcription factor

Schizosaccharomyces pombe

DNA damage

Nucleosome

Fanconi anemia

Nature Communications

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 (CRL4 Wdr70 ) 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 Crb2 53BP1 , decreased Exo1 association and delayed resection. Wdr70 is dispensable for resection upon Crb2 53BP1 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.

CRL4Wdr70 regulates H2B monoubiquitination and facilitates Exo1-dependent resection