title: Unexpected function of the glucanosyltransferase Gas1 in the DNA damage response linked to histone H3 acetyltransferases in Saccharomyces cerevisiae.
abstract: Chromatin organization and structure are crucial for transcriptional regulation, DNA replication, and damage repair. Although initially characterized in remodeling cell wall glucans, the β-1,3-glucanosyltransferase Gas1 was recently discovered to regulate transcriptional silencing in a manner separable from its activity at the cell wall. However, the function of Gas1 in modulating chromatin remains largely unexplored. Our genetic characterization revealed that GAS1 had critical interactions with genes encoding the histone H3 lysine acetyltransferases Gcn5 and Sas3. Specifically, whereas the gas1 gcn5 double mutant was synthetically lethal, deletion of both GAS1 and SAS3 restored silencing in Saccharomyces cerevisiae. The loss of GAS1 also led to broad DNA damage sensitivity with reduced Rad53 phosphorylation and defective cell cycle checkpoint activation following exposure to select genotoxins. Deletion of SAS3 in the gas1 background restored both Rad53 phosphorylation and checkpoint activation following exposure to genotoxins that trigger the DNA replication checkpoint. Our analysis thus uncovers previously unsuspected functions for both Gas1 and Sas3 in DNA damage response and cell cycle regulation.
authors.affiliation: Section of Molecular Biology, Division of Biological Sciences, University of California, San Diego, La Jolla, California 92093-0347.
authors.forename: Moriah
authors.initials: M
authors.lastname: Eustice
authors.forename: Lorraine
authors.initials: L
authors.lastname: Pillus
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000378:metabolism; D064447:Checkpoint Kinase 2 / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly / Q000187:drug effects / Q000528:radiation effects; D004249:DNA Damage / Q000187:drug effects / Q000528:radiation effects; D004260:DNA Repair / Q000187:drug effects / Q000528:radiation effects; D004271:DNA, Fungal / Q000378:metabolism*; D005800:Genes, Fungal; D005804:Genes, Lethal; D051548:Histone Acetyltransferases / Q000235:genetics / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D009153:Mutagens / Q000494:pharmacology; D009154:Mutation; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; C066709:GAS1 protein, S cerevisiae; D008562:Membrane Glycoproteins; D009153:Mutagens; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C526757:SAS3 protein, S cerevisiae; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae
keywords: DNA damage; acetyltransferase; cell cycle checkpoint; chromatin; glucan