title: Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks.
abstract: The cellular response to DNA double-strand breaks (DSBs) is mobilized by the protein kinase ATM, which phosphorylates key players in the DNA damage response (DDR) network. A major question is how ATM controls DSB repair. Optimal repair requires chromatin relaxation at damaged sites. Chromatin reorganization is coupled to dynamic alterations in histone posttranslational modifications. Here, we show that in human cells, DSBs induce monoubiquitylation of histone H2B, a modification that is associated in undamaged cells with transcription elongation. We find that this process relies on recruitment to DSB sites and ATM-dependent phosphorylation of the responsible E3 ubiquitin ligase: the RNF20-RNF40 heterodimer. H2B monoubiquitylation is required for timely recruitment of players in the two major DSB repair pathways-nonhomologous end-joining and homologous recombination repair-and optimal repair via both pathways. Our data and previous data suggest a two-stage model for chromatin decondensation that facilitates DSB repair.
authors.affiliation: The David and Inez Myers Laboratory for Genetic Research, Department of Human Molecular Genetics and Biochemistry, Sackler School of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
authors.forename: Lilach
authors.initials: L
authors.lastname: Moyal
authors.forename: Yaniv
authors.initials: Y
authors.lastname: Lerenthal
authors.forename: Mali
authors.initials: M
authors.lastname: Gana-Weisz
authors.forename: Gilad
authors.initials: G
authors.lastname: Mass
authors.forename: Sairei
authors.initials: S
authors.lastname: So
authors.forename: Shih-Ya
authors.initials: SY
authors.lastname: Wang
authors.forename: Berina
authors.initials: B
authors.lastname: Eppink
authors.forename: Young Min
authors.initials: YM
authors.lastname: Chung
authors.forename: Gil
authors.initials: G
authors.lastname: Shalev
authors.forename: Efrat
authors.initials: E
authors.lastname: Shema
authors.forename: Dganit
authors.initials: D
authors.lastname: Shkedy
authors.forename: Nechama I
authors.initials: NI
authors.lastname: Smorodinsky
authors.forename: Nicole
authors.initials: N
authors.lastname: van Vliet
authors.forename: Bernhard
authors.initials: B
authors.lastname: Kuster
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.forename: Aaron
authors.initials: A
authors.lastname: Ciechanover
authors.forename: Jochen
authors.initials: J
authors.lastname: Dahm-Daphi
authors.forename: Roland
authors.initials: R
authors.lastname: Kanaar
authors.forename: Mickey C-T
authors.initials: MC
authors.lastname: Hu
authors.forename: David J
authors.initials: DJ
authors.lastname: Chen
authors.forename: Moshe
authors.initials: M
authors.lastname: Oren
authors.forename: Yosef
authors.initials: Y
authors.lastname: Shiloh
mesh_terms: D064007:Ataxia Telangiectasia Mutated Proteins; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D020552:Comet Assay / Q000379:methods; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D006367:HeLa Cells; D006657:Histones / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D034622:RNA Interference; D011995:Recombination, Genetic; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D025801:Ubiquitin / Q000737:chemistry*; D044767:Ubiquitin-Protein Ligases / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D004268:DNA-Binding Proteins; D006657:Histones; D025521:Tumor Suppressor Proteins; D025801:Ubiquitin; D044767:Ubiquitin-Protein Ligases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D017346:Protein Serine-Threonine Kinases