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

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

    Research output: Contribution to journalArticle

    37 Citations (Scopus)

    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

    Cite this

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    title = "Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores",
    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.",
    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",
    author = "Patrick Keating and Najma Rachidi and Tanaka, {Tomoyuki U.} and Stark, {Michael J. R.}",
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    doi = "10.1242/jcs.055566",
    language = "English",
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    Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores. / Keating, Patrick; Rachidi, Najma; Tanaka, Tomoyuki U.; Stark, Michael J. R.

    In: Journal of Cell Science, Vol. 122, No. 23, 01.12.2009, p. 4375-4382.

    Research output: Contribution to journalArticle

    TY - JOUR

    T1 - Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores

    AU - Keating, Patrick

    AU - Rachidi, Najma

    AU - Tanaka, Tomoyuki U.

    AU - Stark, Michael J. R.

    PY - 2009/12/1

    Y1 - 2009/12/1

    N2 - 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.

    AB - 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.

    KW - Chromosome bi-orientation

    KW - Microtubules

    KW - Kinetochore

    KW - SPINDLE ASSEMBLY CHECKPOINT

    KW - IPL1/AURORA PROTEIN-KINASE

    KW - CHROMOSOME BI-ORIENTATION

    KW - SACCHAROMYCES-CEREVISIAE

    KW - BUDDING YEAST

    KW - MITOTIC SPINDLE

    KW - MICROTUBULE-BINDING

    KW - RING COMPLEX

    KW - MOLECULAR-MECHANISMS

    KW - DNA-REPLICATION

    U2 - 10.1242/jcs.055566

    DO - 10.1242/jcs.055566

    M3 - Article

    VL - 122

    SP - 4375

    EP - 4382

    JO - Journal of Cell Science

    JF - Journal of Cell Science

    SN - 0021-9533

    IS - 23

    ER -