A role for Saccharomyces cerevisiae histone H2A in DNA repair

Nature. 2000 Dec 21-28;408(6815):1001-4. doi: 10.1038/35050000.

Abstract

Histone proteins associate with and compact eukaryotic nuclear DNA to form chromatin. The basic unit of chromatin is the nucleosome, which is made up of 146 base pairs of DNA wrapped around two of each of four core histones, H2A, H2B, H3 and H4. Chromatin structure and its regulation are important in transcription and DNA replication. We therefore thought that DNA-damage signalling and repair components might also modulate chromatin structure. Here we have characterized a conserved motif in the carboxy terminus of the core histone H2A from Saccharomyces cerevisiae that contains a consensus phosphorylation site for phosphatidylinositol-3-OH kinase related kinases (PIKKs). This motif is important for survival in the presence of agents that generate DNA double-strand breaks, and the phosphorylation of this motif in response to DNA damage is dependent on the PIKK family member Mec1. The motif is not necessary for Mec1-dependent cell-cycle or transcriptional responses to DNA damage, but is required for efficient DNA double-strand break repair by non-homologous end joining. In addition, the motif has a role in determining higher order chromatin structure. Thus, phosphorylation of a core histone in response to DNA damage may cause an alteration of chromatin structure that facilitates DNA repair.

MeSH terms

  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Chromatin / chemistry
  • Chromatin / metabolism
  • DNA Repair*
  • DNA, Fungal / physiology
  • Fungal Proteins / metabolism
  • Histones / genetics
  • Histones / physiology*
  • Humans
  • Intracellular Signaling Peptides and Proteins
  • Molecular Sequence Data
  • Mutagenesis
  • Phosphatidylinositol 3-Kinases / metabolism
  • Phosphorylation
  • Protein-Serine-Threonine Kinases
  • Saccharomyces cerevisiae / genetics*
  • Saccharomyces cerevisiae / physiology
  • Saccharomyces cerevisiae Proteins*

Substances

  • Chromatin
  • DNA, Fungal
  • Fungal Proteins
  • Histones
  • Intracellular Signaling Peptides and Proteins
  • Saccharomyces cerevisiae Proteins
  • Phosphatidylinositol 3-Kinases
  • MEC1 protein, S cerevisiae
  • Protein-Serine-Threonine Kinases
  • TEL1 protein, S cerevisiae