title: Asf1 facilitates dephosphorylation of Rad53 after DNA double-strand break repair.
abstract: To allow for sufficient time to repair DNA double-stranded breaks (DSBs), eukaryotic cells activate the DNA damage checkpoint. In budding yeast, Rad53 (mammalian Chk2) phosphorylation parallels the persistence of the unrepaired DSB and is extinguished when repair is complete in a process termed recovery or when the cells adapt to the DNA damage checkpoint. A strain containing a slowly repaired DSB does not require the histone chaperone Asf1 to resume cell cycle progression after DSB repair. When a second, rapidly repairable DSB is added to this strain, Asf1 becomes required for recovery. Recovery from two repairable DSBs also depends on the histone acetyltransferase Rtt109 and the cullin subunit Rtt101, both of which modify histone H3 that is associated with Asf1. We show that dissociation of histone H3 from Asf1 is required for efficient recovery and that Asf1 is required for complete dephosphorylation of Rad53 when the upstream DNA damage checkpoint signaling is turned off. Our data suggest that the requirements for recovery from the DNA damage checkpoint become more stringent with increased levels of damage and that Asf1 plays a histone chaperone-independent role in facilitating complete Rad53 dephosphorylation following repair.
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Tsabar
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: David P
authors.initials: DP
authors.lastname: Waterman
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Fiona
authors.initials: F
authors.lastname: Aguilar
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Lizabeth
authors.initials: L
authors.lastname: Katsnelson
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Vinay V
authors.initials: VV
authors.lastname: Eapen
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: Gonen
authors.initials: G
authors.lastname: Memisoglu
authors.affiliation: Department of Biology, Rosenstiel Basic Medical Sciences Research Center, Brandeis University, Waltham, Massachusetts 02454, USA.
authors.forename: James E
authors.initials: JE
authors.lastname: Haber
mesh_terms: D059447:Cell Cycle Checkpoints; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D064447:Checkpoint Kinase 2 / Q000378:metabolism*; D044842:Cullin Proteins / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D051548:Histone Acetyltransferases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D012441:Saccharomyces cerevisiae / Q000201:enzymology / Q000235:genetics / Q000502:physiology*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C109731:ASF1 protein, S cerevisiae; D018797:Cell Cycle Proteins; D044842:Cullin Proteins; D006657:Histones; D018832:Molecular Chaperones; C476451:RTT101 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D051548:Histone Acetyltransferases; C517120:Rtt109 protein, S cerevisiae; D064447:Checkpoint Kinase 2; C067022:RAD53 protein, S cerevisiae
keywords: Asf1; DNA damage checkpoint; DNA double-stranded breaks; Rad53; Rtt101; Rtt109