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.

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