DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A

Steven Bergink; Florian A Salomons; Deborah Hoogstraten; Tom A M Groothuis; Harm de Waard; Junxin Wu; Li Yuan; Elisabetta Citterio; Adriaan B Houtsmuller; Jacques Neefjes; Jan H J Hoeijmakers; Wim Vermeulen; Nico P Dantuma

doi:10.1101/gad.373706

DNA damage triggers nucleotide excision repair-dependent monoubiquitylation of histone H2A

Genes Dev. 2006 May 15;20(10):1343-52. doi: 10.1101/gad.373706.

Authors

Steven Bergink¹, Florian A Salomons, Deborah Hoogstraten, Tom A M Groothuis, Harm de Waard, Junxin Wu, Li Yuan, Elisabetta Citterio, Adriaan B Houtsmuller, Jacques Neefjes, Jan H J Hoeijmakers, Wim Vermeulen, Nico P Dantuma

Affiliation

¹ MGC Department of Cell Biology and Genetics, Center for Biomedical Genetics, Erasmus Medical Center, Rotterdam, The Netherlands.

Abstract

Chromatin changes within the context of DNA repair remain largely obscure. Here we show that DNA damage induces monoubiquitylation of histone H2A in the vicinity of DNA lesions. Ultraviolet (UV)-induced monoubiquitylation of H2A is dependent on functional nucleotide excision repair and occurs after incision of the damaged strand. The ubiquitin ligase Ring2 is required for the DNA damage-induced H2A ubiquitylation. UV-induced ubiquitylation of H2A is dependent on the DNA damage signaling kinase ATR (ATM- and Rad3-related) but not the related kinase ATM (ataxia telangiectasia-mutated). Although the response coincides with phosphorylation of variant histone H2AX, H2AX was not required for H2A ubiquitylation. Together our data show that monoubiquitylation of H2A forms part of the cellular response to UV damage and suggest a role of this modification in DNA repair-induced chromatin remodeling.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Ataxia Telangiectasia Mutated Proteins
Cell Cycle Proteins / genetics
Cell Cycle Proteins / metabolism
Cell Nucleus / metabolism
Cells, Cultured
DNA / radiation effects
DNA Damage*
DNA Repair*
Histones / metabolism*
Humans
Liver X Receptors
Molecular Sequence Data
Orphan Nuclear Receptors
Proteasome Endopeptidase Complex / metabolism
Protein Serine-Threonine Kinases / genetics
Protein Serine-Threonine Kinases / metabolism
Receptors, Cytoplasmic and Nuclear / genetics
Receptors, Cytoplasmic and Nuclear / metabolism
Tumor Suppressor Proteins / genetics
Tumor Suppressor Proteins / metabolism*
Ubiquitin / metabolism*
Ubiquitin Thiolesterase / genetics
Ubiquitin Thiolesterase / metabolism*
Ultraviolet Rays

Substances

BAP1 protein, human
Cell Cycle Proteins
Histones
Liver X Receptors
Orphan Nuclear Receptors
Receptors, Cytoplasmic and Nuclear
Tumor Suppressor Proteins
Ubiquitin
DNA
ATR protein, human
Ataxia Telangiectasia Mutated Proteins
Protein Serine-Threonine Kinases
Ubiquitin Thiolesterase
Proteasome Endopeptidase Complex