title: A DNA polymerase alpha accessory protein, Mcl1, is required for propagation of centromere structures in fission yeast.
abstract: Specialized chromatin exists at centromeres and must be precisely transmitted during DNA replication. The mechanisms involved in the propagation of these structures remain elusive. Fission yeast centromeres are composed of two chromatin domains: the central CENP-A(Cnp1) kinetochore domain and flanking heterochromatin domains. Here we show that fission yeast Mcl1, a DNA polymerase alpha (Pol alpha) accessory protein, is critical for maintenance of centromeric chromatin. In a screen for mutants that alleviate both central domain and outer repeat silencing, we isolated several cos mutants, of which cos1 is allelic to mcl1. The mcl1-101 mutation causes reduced CENP-A(Cnp1) in the central domain and an aberrant increase in histone acetylation in both domains. These phenotypes are also observed in a mutant of swi7(+), which encodes a catalytic subunit of Pol alpha. Mcl1 forms S-phase-specific nuclear foci, which colocalize with those of PCNA and Pol alpha. These results suggest that Mcl1 and Pol alpha are required for propagation of centromere chromatin structures during DNA replication.
authors.affiliation: Division of Mutagenesis, National Institute of Genetics, Mishima, Shizuoka, Japan.
authors.forename: Toyoaki
authors.initials: T
authors.lastname: Natsume
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Tsutsui
authors.forename: Takashi
authors.initials: T
authors.lastname: Sutani
authors.forename: Elaine M
authors.initials: EM
authors.lastname: Dunleavy
authors.forename: Alison L
authors.initials: AL
authors.lastname: Pidoux
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Katsuhiko
authors.initials: K
authors.lastname: Shirahige
authors.forename: Robin C
authors.initials: RC
authors.lastname: Allshire
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Yamao
mesh_terms: D000107:Acetylation; D002503:Centromere; D047369:Chromatin Immunoprecipitation; D015825:Chromosomes, Fungal; D003001:Cloning, Molecular; D004256:DNA Polymerase I / Q000378:metabolism*; D020868:Gene Silencing; D006655:Histone Deacetylases / Q000235:genetics; D006657:Histones / Q000378:metabolism; D008856:Microscopy, Fluorescence; D009154:Mutation; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D012568:Schizosaccharomyces / Q000201:enzymology / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure*
chemical_list: D006657:Histones; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D019253:Proto-Oncogene Proteins c-bcl-2; D004256:DNA Polymerase I; D006655:Histone Deacetylases