title: The INO80 chromatin remodeling complex prevents polyploidy and maintains normal chromatin structure at centromeres.
abstract: The INO80 chromatin remodeling complex functions in transcriptional regulation, DNA repair, and replication. Here we uncover a novel role for INO80 in regulating chromosome segregation. First, we show that the conserved Ies6 subunit is critical for INO80 function in vivo. Strikingly, we found that loss of either Ies6 or the Ino80 catalytic subunit results in rapid increase in ploidy. One route to polyploidy is through chromosome missegregation due to aberrant centromere structure, and we found that loss of either Ies6 or Ino80 leads to defective chromosome segregation. Importantly, we show that chromatin structure flanking centromeres is altered in cells lacking these subunits and that these alterations occur not in the Cse4-containing centromeric nucleosome, but in pericentric chromatin. We provide evidence that these effects are mediated through misincorporation of H2A.Z, and these findings indicate that H2A.Z-containing pericentric chromatin, as in higher eukaryotes with regional centromeres, is important for centromere function in budding yeast. These data reveal an important additional mechanism by which INO80 maintains genome stability.
authors.affiliation: MRC Genome Damage and Stability Centre, University of Sussex, Brighton BN1 9RQ, United Kingdom.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Chambers
authors.forename: Georgina
authors.initials: G
authors.lastname: Ormerod
authors.forename: Samuel C
authors.initials: SC
authors.lastname: Durley
authors.forename: Tina L
authors.initials: TL
authors.lastname: Sing
authors.forename: Grant W
authors.initials: GW
authors.lastname: Brown
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Kent
authors.forename: Jessica A
authors.initials: JA
authors.lastname: Downs
mesh_terms: D002503:Centromere / Q000737:chemistry / Q000378:metabolism*; D002843:Chromatin / Q000737:chemistry*; D042002:Chromatin Assembly and Disassembly; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D020090:Chromosome Segregation; D004249:DNA Damage; D015966:Gene Expression Regulation, Fungal; D006657:Histones / Q000235:genetics; D009154:Mutation; D011123:Polyploidy; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D006657:Histones; C493530:Htz1 protein, S cerevisiae; C483404:INO80 complex, S cerevisiae; C000609268:Ies6 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins