title: Asf1 links Rad53 to control of chromatin assembly.
abstract: Yeast defective in the checkpoint kinase Rad53 fail to recover from transient DNA replication blocks and synthesize intact chromosomes. The effectors of Rad53 relevant to this recovery process are unknown. Here we report that overproduction of the chromatin assembly factor Asf1 can suppress the Ts phenotype of mrc1rad53 double mutants and the HU sensitivity of rad53 mutants. Eliminating silencing also suppresses this lethality, further implicating chromatin structure in checkpoint function. We find that Asf1 and Rad53 exist in a dynamic complex that dissociates in response to replication blocks and DNA damage. Thus, checkpoint pathways directly regulate chromatin assembly to promote survival in response to DNA damage and replication blocks.
authors.affiliation: Verna and Mars McLean Department of Biochemistry and Molecular Biology, Howard Hughes Medical Institute, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: F
authors.initials: F
authors.lastname: Hu
authors.forename: A A
authors.initials: AA
authors.lastname: Alcasabas
authors.forename: S J
authors.initials: SJ
authors.lastname: Elledge
mesh_terms: D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2; D002843:Chromatin / Q000378:metabolism*; D004249:DNA Damage; D004261:DNA Replication; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D015966:Gene Expression Regulation, Fungal; D020868:Gene Silencing; D005804:Genes, Lethal; D016153:Genes, Suppressor; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D029701:Saccharomyces cerevisiae Proteins; D013696:Temperature; D015003:Yeasts / Q000166:cytology / Q000187:drug effects / Q000235:genetics
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002843:Chromatin; D005656:Fungal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D018832:Molecular Chaperones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D011494:Protein Kinases; D064447:Checkpoint Kinase 2; C088937:MEC1 protein, S cerevisiae; D017346:Protein Serine-Threonine Kinases; C067022:RAD53 protein, S cerevisiae