Kinetochores coordinate pericentromeric cohesion and early DNA replication by Cdc7-Dbf4 kinase recruitment

Toyoaki Natsume, Carolin A. Müller, Yuki Katou, Renata Retkute, Marek Gierlinski, Hiroyuki Araki, J. Julian Blow, Katsuhiko Shirahige, Conrad A. Nieduszynski, Tomoyuki U. Tanaka (Lead / Corresponding author)

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    82 Citations (Scopus)

    Abstract

    Centromeres play several important roles in ensuring proper chromosome segregation. Not only do they promote kinetochore assembly for microtubule attachment, but they also support robust sister chromatid cohesion at pericentromeres and facilitate replication of centromeric DNA early in S phase. However, it is still elusive how centromeres orchestrate all these functions at the same site. Here, we show that the budding yeast Dbf4-dependent kinase (DDK) accumulates at kinetochores in telophase, facilitated by the Ctf19 kinetochore complex. This promptly recruits Sld3-Sld7 replication initiator proteins to pericentromeric replication origins so that they initiate replication early in S phase. Furthermore, DDK at kinetochores independently recruits the Scc2-Scc4 cohesin loader to centromeres in G1 phase. This enhances cohesin loading and facilitates robust pericentromeric cohesion in S phase. Thus, we have found the central mechanism by which kinetochores orchestrate early S phase DNA replication and robust sister chromatid cohesion at microtubule attachment sites.

    Original languageEnglish
    Pages (from-to)661-674
    Number of pages14
    JournalMolecular Cell
    Volume50
    Issue number5
    DOIs
    Publication statusPublished - 6 Jun 2013

    Keywords

    • YEAST GENOME
    • SISTER CHROMATIDS
    • S-PHASE
    • CELL IMAGING REVEALS
    • HETEROCHROMATIN
    • ASSOCIATION
    • EUKARYOTIC CELLS
    • SACCHAROMYCES-CEREVISIAE
    • CHROMOSOME-REPLICATION
    • XENOPUS EGG EXTRACTS

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