title: Polo kinase Cdc5 associates with centromeres to facilitate the removal of centromeric cohesin during mitosis.
abstract: Sister chromatid cohesion is essential for tension-sensing mechanisms that monitor bipolar attachment of replicated chromatids in metaphase. Cohesion is mediated by the association of cohesins along the length of sister chromatid arms. In contrast, centromeric cohesin generates intrastrand cohesion and sister centromeres, while highly cohesin enriched, are separated by >800 nm at metaphase in yeast. Removal of cohesin is necessary for sister chromatid separation during anaphase, and this is regulated by evolutionarily conserved polo-like kinase (Cdc5 in yeast, Plk1 in humans). Here we address how high levels of cohesins at centromeric chromatin are removed. Cdc5 associates with centromeric chromatin and cohesin-associated regions. Maximum enrichment of Cdc5 in centromeric chromatin occurs during the metaphase-to-anaphase transition and coincides with the removal of chromosome-associated cohesin. Cdc5 interacts with cohesin in vivo, and cohesin is required for association of Cdc5 at centromeric chromatin. Cohesin removal from centromeric chromatin requires Cdc5 but removal at distal chromosomal arm sites does not. Our results define a novel role for Cdc5 in regulating removal of centromeric cohesins and faithful chromosome segregation.
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Mishra
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Sultan
authors.initials: S
authors.lastname: Ciftci-Yilmaz
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: David
authors.initials: D
authors.lastname: Reynolds
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Au
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Lars
authors.initials: L
authors.lastname: Boeckmann
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Dittman
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Ziad
authors.initials: Z
authors.lastname: Jowhar
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892.
authors.forename: Tejaswini
authors.initials: T
authors.lastname: Pachpor
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Elaine
authors.initials: E
authors.lastname: Yeh
authors.affiliation: Department of Microbiology and Physiological Systems, University of Massachusetts Medical School, Worcester, MA 01655.
authors.forename: Richard E
authors.initials: RE
authors.lastname: Baker
authors.affiliation: Department of Biology, Johns Hopkins University, Baltimore, MD 21218.
authors.forename: M Andrew
authors.initials: MA
authors.lastname: Hoyt
authors.affiliation: Institute for Research in Immunology and Cancer and Département de Pathologie et Biologie Cellulaire, Université de Montréal, Montreal, QC H3C 3J7, Canada.
authors.forename: Damien
authors.initials: D
authors.lastname: D'Amours
authors.affiliation: Department of Biology, University of North Carolina, Chapel Hill, NC 27599.
authors.forename: Kerry
authors.initials: K
authors.lastname: Bloom
authors.affiliation: Genetics Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892 basraim@nih.gov.
authors.forename: Munira A
authors.initials: MA
authors.lastname: Basrai
mesh_terms: D000705:Anaphase; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002503:Centromere / Q000201:enzymology / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D020090:Chromosome Segregation; D008677:Metaphase; D008938:Mitosis / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology* / Q000201:enzymology* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D000097722:Cohesins; D000097869:Polo-Like Kinase 1
chemical_list: D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D029701:Saccharomyces cerevisiae Proteins; D000097722:Cohesins; D000097869:Polo-Like Kinase 1; C081927:CDC5 protein, S cerevisiae