title: The budding yeast silencing protein Sir1 is a functional component of centromeric chromatin.
abstract: In fission yeast and multicellular organisms, centromere-proximal regions of chromosomes are heterochromatic, containing proteins that silence gene expression. In contrast, the relationship between heterochromatin proteins and kinetochore function in the budding yeast Saccharomyces cerevisiae remains largely unexplored. Here we report that the yeast heterochromatin protein Sir1 is a component of centromeric chromatin and contributes to mitotic chromosome stability. Sir1 recruitment to centromeres occurred through a novel mechanism independent of its interaction with the origin recognition complex (ORC). Sir1 function at centromeres was distinct from its role in forming heterochromatin, because the Sir2-4 proteins were not associated with centromeric regions. Sir1 bound to Cac1, a subunit of chromatin assembly factor I (CAF-I), and helped to retain Cac1 at centromeric loci. These studies reveal that although budding yeast and mammalian cells use fundamentally different mechanisms of forming heterochromatin, they both use silencing proteins to attract the histone deposition factor CAF-I to centromeric chromatin.
authors.affiliation: Lawrence Berkeley National Laboratory and Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California 94720, USA.
authors.forename: Judith A
authors.initials: JA
authors.lastname: Sharp
authors.forename: Denise C
authors.initials: DC
authors.lastname: Krawitz
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Gardner
authors.forename: Catherine A
authors.initials: CA
authors.lastname: Fox
authors.forename: Paul D
authors.initials: PD
authors.lastname: Kaufman
mesh_terms: D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002503:Centromere / Q000235:genetics / Q000378:metabolism*; D002843:Chromatin / Q000378:metabolism*; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics / Q000378:metabolism; D018386:Kinetochores / Q000502:physiology; D064246:Mad2 Proteins; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D004718:Saccharomycetales / Q000235:genetics*; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*
chemical_list: C081071:CBF2 protein, S cerevisiae; D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D056504:Chromatin Assembly Factor-1; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C078808:HIR1 protein, S cerevisiae; C577695:MAD2 protein, S cerevisiae; D064246:Mad2 Proteins; D009687:Nuclear Proteins; D021122:Protein Subunits; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C084121:SIR1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D038281:Silent Information Regulator Proteins, Saccharomyces cerevisiae