title: Chromatin assembly factors Asf1 and CAF-1 have overlapping roles in deactivating the DNA damage checkpoint when DNA repair is complete.
abstract: In response to a DNA double-strand break (DSB), chromatin is rapidly modified by the damage dependent checkpoint kinases. Also, disassembly of chromatin occurs at the break site. The damage-induced modification of chromatin structure is involved in the maintenance of the checkpoint. However, it has not been determined how chromatin is restored to its undamaged state when DSB repair is complete. Here, we show the involvement of two chromatin assembly factors (CAFs), Asf1 and CAF-1, in turning off the DNA damage checkpoint in budding yeast. DSB repair or formation of gamma-H2AX does not depend on either the CAF-1 protein, Cac1, or Asf1. Absence of these proteins does not impair the ability of cells to resume cell cycle progression in the presence of an unrepaired DSB (adaptation). However, recovery from cell cycle checkpoint arrest when the DSB is repaired by gene conversion is substantially defective in the absence of both CAF-1 and Asf1, whereas deleting CAC1 or ASF1 individually had little effect. We suggest that CAF-1 and Asf1 function redundantly to deactivate the checkpoint by restoring chromatin structure on the completion of DSB repair.
authors.affiliation: Rosenstiel Center and Department of Biology, Brandeis University, Waltham, MA 02454-9110, USA.
authors.forename: Jung-Ae
authors.initials: JA
authors.lastname: Kim
authors.forename: James E
authors.initials: JE
authors.lastname: Haber
mesh_terms: D000222:Adaptation, Physiological; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000378:metabolism*; D056504:Chromatin Assembly Factor-1; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D053903:DNA Breaks, Double-Stranded; D004249:DNA Damage; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004720:Endonucleases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D050296:Microbial Viability; D018832:Molecular Chaperones / Q000378:metabolism*; D009707:Nucleosomes / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D006657:Histones; D018832:Molecular Chaperones; D009707:Nucleosomes; C533589:RLF2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; C507778:gammaH2AX protein, S cerevisiae; D004720:Endonucleases