title: Methylation of histone H3 lysine-79 by Dot1p plays multiple roles in the response to UV damage in Saccharomyces cerevisiae.
abstract: Various proteins have been found to play roles in both the repair of UV damaged DNA and heterochromatin-mediated silencing in the yeast Saccharomyces cerevisiae. In particular, factors that are involved in the methylation of lysine-79 of histone H3 by Dot1p have been implicated in both processes, suggesting a bipartite function for this modification. We find that a dot1 null mutation and a histone H3 point mutation at lysine-79 cause increased sensitivity to UV radiation, suggesting that lysine-79 methylation is important for efficient repair of UV damage. Epistasis analysis between dot1 and various UV repair genes indicates that lysine-79 methylation plays overlapping roles within the nucleotide excision, post-replication and recombination repair pathways, as well as RAD9-mediated checkpoint function. In contrast, epistasis analysis with the H3 lysine-79 point mutation indicates that the lysine-to-glutamic acid substitution exerts specific effects within the nucleotide excision repair and post-replication repair pathways, suggesting that this allele only disrupts a subset of the functions of lysine-79 methylation. The overall results indicate the existence of distinct and separable roles of histone H3 lysine-79 methylation in the response to UV damage, potentially serving to coordinate the various repair processes.
authors.affiliation: Department of Biology, Denison University, 213 Talbot Hall, Granville, Ohio 43023, USA.
authors.forename: Lindsey J
authors.initials: LJ
authors.lastname: Bostelman
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Keller
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Albrecht
authors.forename: Arzu
authors.initials: A
authors.lastname: Arat
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Thompson
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004249:DNA Damage; D004265:DNA Helicases; D004260:DNA Repair; D004261:DNA Replication / Q000502:physiology; D004307:Dose-Response Relationship, Radiation; D011495:Histone-Lysine N-Methyltransferase / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008239:Lysine / Q000378:metabolism*; D008745:Methylation; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D011839:Radiation, Ionizing; D011995:Recombination, Genetic / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000378:metabolism / Q000528:radiation effects; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D014466:Ultraviolet Rays
chemical_list: D018797:Cell Cycle Proteins; D006657:Histones; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C069930:rad9 protein; D004247:DNA; C416235:Dot1 protein, S cerevisiae; D011495:Histone-Lysine N-Methyltransferase; D000251:Adenosine Triphosphatases; C076225:RAD5 protein, S cerevisiae; D004265:DNA Helicases; D008239:Lysine