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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 language | English |
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Pages (from-to) | 4375-4382 |
Number of pages | 8 |
Journal | Journal of Cell Science |
Volume | 122 |
Issue number | 23 |
DOIs | |
Publication status | Published - 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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Dive into the research topics of 'Ipl1-dependent phosphorylation of Dam1 is reduced by tension applied on kinetochores'. Together they form a unique fingerprint.Projects
- 2 Finished
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Aref#d: 20039. Mechanisms Ensuring Sister Kinetochore Bi-Orientation on the Mitotic Spindle (Programme Grant)
Tanaka, T. (Investigator)
1/12/08 → 31/05/14
Project: Research
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Aref#d: 19770. Division of Gene Regulation and Expression Strategic Award
Blow, J. (Investigator), Hutvagner, G. (Investigator), Lamond, A. (Investigator), Owen-Hughes, T. (Investigator) & Swedlow, J. (Investigator)
1/01/08 → 31/12/12
Project: Research