Saccharomyces cerevisiae histone H2A Ser122 facilitates DNA repair.
DNA repair takes place in the context of chromatin. Recently, it has become apparent that proteins that make up and modulate chromatin structure are involved in the detection and repair of DNA lesions. We previously demonstrated that Ser129 in the carboxyl-terminal tail of yeast histone H2A is important for double-strand-break responses. By undertaking a systematic site-directed mutagenesis approach, we identified another histone H2A serine residue (Ser122) that is important for survival in the presence of DNA-damaging agents. We show that mutation of this residue does not affect DNA damage-dependent Rad53 phosphorylation or G(2)/M checkpoint responses. Interestingly, we find that yeast lacking H2A S122 are defective in their ability to sporulate. Finally, we demonstrate that H2A S122 provides a function distinct from that of H2A S129. These data demonstrate a role for H2A S122 in facilitating survival in the presence of DNA damage and suggest a potential role in mediating homologous recombination. The distinct roles of H2A S122 and S129 in mediating these responses suggest that chromatin components can provide specialized functions for distinct DNA repair and survival mechanisms and point toward the possibility of a complex DNA damage responsive histone code.
Harvey
Anne C
AC
Department of Biochemistry, University of Cambridge, UK.
Jackson
Stephen P
SP
Downs
Jessica A
JA
D000595:Amino Acid Sequence; D015153:Blotting, Western; D018797:Cell Cycle Proteins / Q000378:metabolism; D002455:Cell Division; D064447:Checkpoint Kinase 2; D002843:Chromatin / Q000378:metabolism; D047369:Chromatin Immunoprecipitation; D004260:DNA Repair; D016195:G2 Phase; D006657:Histones / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D008836:Micrococcal Nuclease / Q000378:metabolism; D008969:Molecular Sequence Data; D009154:Mutation; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D012694:Serine / Q000737:chemistry; D013997:Time Factors
D018797:Cell Cycle Proteins; D002843:Chromatin; D006657:Histones; D029701:Saccharomyces cerevisiae Proteins; D012694:Serine; D064447:Checkpoint Kinase 2; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae; D008836:Micrococcal Nuclease