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Cell and Developmental Biology Programme Miquel Rosas Salvans

Cell and Developmental Biology Programme Miquel Rosas SalvansCell and Developmental Biology Programme Miquel Rosas Salvans

16/05/2022
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Cell and Developmental Biology Programme Miquel Rosas Salvans

MARIE CURIE

16/05/202210:00MARIE CURIECell and Developmental Biology ProgrammeMiquel Rosas SalvansUniversity of California, San Francisco (UCSF), Dept of bioengineering and therapeutic science, Dumont labThe Astrin-SKAP Complex Lubricates the Mammalian Kinetochore-Microtubule InterfaceHost: Vernos, IsabelleAbstract:Summary:

Each time a cell divides, it must equally distribute its genetic material to its daughter cells. The kinetochore is the large protein complex that links chromosomes to dynamic spindle microtubules to move and segregate them. While we know nearly all mammalian kinetochore proteins, how these give rise to dynamic yet strong microtubule attachments remains poorly understood. In this talk, I will focus on the Astrin-SKAP complex, which localizes to bioriented kinetochores and is essential to chromosome segregation, but whose mechanical role is unclear. Using live imaging, we find that SKAP depletion dampens metaphase kinetochore movements, reduces sister kinetochore coordination and increases the tension between sisters. Using laser ablation to isolate kinetochores bound to polymerizing vs depolymerizing microtubules, we show that without SKAP kinetochores move slower on both polymerizing and depolymerizing microtubules, and that more force is needed to rescue microtubules to polymerize. Thus, in contrast to previously described kinetochore proteins that increase the grip on microtubules under force, Astrin-SKAP reduces grip, lowering friction. Together, our findings suggest a model where the Astrin-SKAP complex effectively “lubricates” correct, bioriented attachments to help preserve them and ensure a smooth chromosome movement and faithful segregation.