COMMD4 Functions with the Histone H2A-H2B Dimer for the Timely Repair of DNA Double-strand Breaks

Overview

Journal Commun Biol

Specialty Biology

Date 2021 Apr 20

PMID 33875784

Citations 9

Authors

Amila Suraweera

Neha S Gandhi

Sam Beard

Joshua T Burgess

Laura V Croft

Emma Bolderson

Ali Naqi

Nicholas W Ashton

Mark N Adams

Kienan I Savage

Shu-Dong Zhang

Kenneth J OByrne

Derek J Richard

Affiliations

Soon will be listed here.

Abstract

Genomic stability is critical for normal cellular function and its deregulation is a universal hallmark of cancer. Here we outline a previously undescribed role of COMMD4 in maintaining genomic stability, by regulation of chromatin remodelling at sites of DNA double-strand breaks. At break-sites, COMMD4 binds to and protects histone H2B from monoubiquitination by RNF20/RNF40. DNA damage-induced phosphorylation of the H2A-H2B heterodimer disrupts the dimer allowing COMMD4 to preferentially bind H2A. Displacement of COMMD4 from H2B allows RNF20/40 to monoubiquitinate H2B and for remodelling of the break-site. Consistent with this critical function, COMMD4-deficient cells show excessive elongation of remodelled chromatin and failure of both non-homologous-end-joining and homologous recombination. We present peptide-mapping and mutagenesis data for the potential molecular mechanisms governing COMMD4-mediated chromatin regulation at DNA double-strand breaks.

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