Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores

Patrick Keating, Najma Rachidi, Tomoyuki U. Tanaka, Michael J. R. Stark

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    Abstract

    The conserved Aurora B protein kinase (Ipl1 in Saccharomyces cerevisiae) is essential for ensuring that sister kinetochores become attached to microtubules from opposite spindle poles (bi-orientation) before anaphase onset. When sister chromatids become attached to microtubules from a single pole, Aurora B/Ipl1 facilitates turnover of kinetochore-microtubule attachments. This process requires phosphorylation by Aurora B/Ipl1 of kinetochore components such as Dam1 in yeast. Once bi-orientation is established and tension is applied on kinetochores, Aurora B/Ipl1 must stop promoting this turnover, otherwise correct attachment would never be stabilised. How this is achieved remains elusive: it might be due to dephosphorylation of Aurora B/Ipl1 substrates at kinetochores, or might take place independently, for example because of conformational changes in kinetochores. Here, we show that Ipl1-dependent phosphorylation at crucial sites on Dam1 is maximal during S phase and minimal during metaphase, matching the cell cycle window when chromosome bi-orientation occurs. Intriguingly, when we reduced tension at kinetochores through failure to establish sister chromatid cohesion, Dam1 phosphorylation persisted in metaphase-arrested cells. We propose that Aurora B/Ipl1-facilitated bi-orientation is stabilised in response to tension at kinetochores by dephosphorylation of Dam1, resulting in termination of kinetochore-microtubule attachment turnover.

    Original languageEnglish
    Pages (from-to)4375-4382
    Number of pages8
    JournalJournal of Cell Science
    Volume122
    Issue number23
    DOIs
    Publication statusPublished - 1 Dec 2009

    Keywords

    • Chromosome bi-orientation
    • Microtubules
    • Kinetochore
    • SPINDLE ASSEMBLY CHECKPOINT
    • IPL1/AURORA PROTEIN-KINASE
    • CHROMOSOME BI-ORIENTATION
    • SACCHAROMYCES-CEREVISIAE
    • BUDDING YEAST
    • MITOTIC SPINDLE
    • MICROTUBULE-BINDING
    • RING COMPLEX
    • MOLECULAR-MECHANISMS
    • DNA-REPLICATION

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