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dc.contributor.authorSharp, Judith A.
dc.contributor.authorRizki, Gizem
dc.contributor.authorKaufman, Paul D.
dc.date2022-08-11T08:10:15.000
dc.date.accessioned2022-08-23T17:01:01Z
dc.date.available2022-08-23T17:01:01Z
dc.date.issued2005-11-16
dc.date.submitted2011-04-19
dc.identifier.citationGenetics. 2005 Nov;171(3):885-99. Epub 2005 Jul 14. <a href="http://dx.doi.org/10.1534/genetics.105.044719">Link to article on publisher's site</a>
dc.identifier.issn0016-6731 (Linking)
dc.identifier.doi10.1534/genetics.105.044719
dc.identifier.pmid16020781
dc.identifier.urihttp://hdl.handle.net/20.500.14038/43915
dc.description.abstractCAF-1, Hir proteins, and Asf1 are histone H3/H4 binding proteins important for chromatin-mediated transcriptional silencing. We explored genetic and physical interactions between these proteins and S-phase/DNA damage checkpoint kinases in the budding yeast Saccharomyces cerevisiae. Although cells lacking checkpoint kinase Mec1 do not display defects in telomeric gene silencing, silencing was dramatically reduced in cells lacking both Mec1 and the Cac1 subunit of CAF-1. Silencing was restored in cac1Delta and cac1Delta mec1Delta cells upon deletion of Rad53, the kinase downstream of Mec1. Restoration of silencing to cac1Delta cells required both Hir1 and Asf1, suggesting that Mec1 counteracts functional sequestration of the Asf1/Hir1 complex by Rad53. Consistent with this idea, the degree of suppression of silencing defects by rad53 alleles correlated with effects on Asf1 binding. Furthermore, deletion of the Dun1 kinase, a downstream target of Rad53, also suppressed the silencing defects of cac1Delta cells and reduced the levels of Asf1 associated with Rad53 in vivo. Loss of Mec1 and Rad53 did not alter telomere lengths or Asf1 protein levels, nuclear localization, or chromosome association. We conclude that the Mec1 and Dun1 checkpoint kinases regulate the Asf1-Rad53 interaction and therefore affect the activity of the Asf1/Hir complex in vivo.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16020781&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1534/genetics.105.044719
dc.subjectCell Cycle Proteins
dc.subjectDNA Damage
dc.subjectEpistasis, Genetic
dc.subjectGene Silencing
dc.subjectHistones
dc.subjectIntracellular Signaling Peptides and Proteins
dc.subjectMolecular Chaperones
dc.subjectMutation
dc.subjectNuclear Proteins
dc.subjectProtein Kinases
dc.subjectProtein Structure, Tertiary
dc.subjectProtein-Serine-Threonine Kinases
dc.subjectRepressor Proteins
dc.subjectSaccharomyces cerevisiae
dc.subjectSaccharomyces cerevisiae Proteins
dc.subjectGenetics and Genomics
dc.titleRegulation of histone deposition proteins Asf1/Hir1 by multiple DNA damage checkpoint kinases in Saccharomyces cerevisiae
dc.typeJournal Article
dc.source.journaltitleGenetics
dc.source.volume171
dc.source.issue3
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/pgfe_pp/126
dc.identifier.contextkey1946781
html.description.abstract<p>CAF-1, Hir proteins, and Asf1 are histone H3/H4 binding proteins important for chromatin-mediated transcriptional silencing. We explored genetic and physical interactions between these proteins and S-phase/DNA damage checkpoint kinases in the budding yeast Saccharomyces cerevisiae. Although cells lacking checkpoint kinase Mec1 do not display defects in telomeric gene silencing, silencing was dramatically reduced in cells lacking both Mec1 and the Cac1 subunit of CAF-1. Silencing was restored in cac1Delta and cac1Delta mec1Delta cells upon deletion of Rad53, the kinase downstream of Mec1. Restoration of silencing to cac1Delta cells required both Hir1 and Asf1, suggesting that Mec1 counteracts functional sequestration of the Asf1/Hir1 complex by Rad53. Consistent with this idea, the degree of suppression of silencing defects by rad53 alleles correlated with effects on Asf1 binding. Furthermore, deletion of the Dun1 kinase, a downstream target of Rad53, also suppressed the silencing defects of cac1Delta cells and reduced the levels of Asf1 associated with Rad53 in vivo. Loss of Mec1 and Rad53 did not alter telomere lengths or Asf1 protein levels, nuclear localization, or chromosome association. We conclude that the Mec1 and Dun1 checkpoint kinases regulate the Asf1-Rad53 interaction and therefore affect the activity of the Asf1/Hir complex in vivo.</p>
dc.identifier.submissionpathpgfe_pp/126
dc.contributor.departmentProgram in Gene Function and Expression
dc.source.pages885-99


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