Mr Graham Buttrick, Research Fellow in the Biomedical Cell Biology Division at Warwick, will present this seminar, speaking on 'Promoting kinetochore attachment after anaphase onset'.

Abstract

The microtubule-based link between kinetochores and centrosomes must be precisely regulated during mitosis for equal chromosome segregation into daughter cells. In fission yeast, kinetochores remain attached to the centrosome equivalent, the spindle pole body (SPB), throughout the cell cycle. During mitosis, the Aurora-B related kinase, Ark1, and the opposing PP1-type phosphatase Dis2 regulate kinetochore attachments.

To uncover novel factors required for chromosome segregation, we performed a genetic screen for deletions that exacerbated the growth defect of Ddis2 cells, and identified nsk1. Initial analyses indicate that Dnsk1 cells have a checkpoint-mediated delay in mitosis, and a significant rate of chromosome mis-segregation. Consistent with a role in chromosome segregation, Nsk1 colocalises with kinetochores and SPBs. Surprisingly, this localisation is repressed by phosphorylation during prometaphase and metaphase. Dephosphorylation by the Cdc14-related phosphatase Clp1 allows Nsk1 to colocalise with kinetochores and SPBs only after anaphase onset. We used live imaging to determine how Nsk1 could be required for correct chromosome segregation and timely anaphase onset despite only associating with kinetochores in anaphase.

Interestingly, we found that Nsk1 is required for stable kinetochore-SPB interactions during anaphase. In the absence of Nsk1, kinetochores frequently detach from SPBs during anaphase. When this happens late in anaphase B, chromosome segregation is unaffected, but the detached kinetochore must be recaptured during the following prometaphase, causing a checkpoint-mediated delay. Occasionally, kinetochores become detached earlier in anaphase, leading to the observed low rate of chromosome missegregation.

Further information

All staff and students are welcome and there is no need to register in advance. If you have any queries, please contact Gemma Wild at G dot Wild at warwick dot ac dot uk

This research seminar is part of the Biomedical Cell Biology Seminar series, presented by the Division of Biomedical Cell Biology, Warwick Medical School.