PRBB-CRG Sessions Sophie Dumont

21/04/202312:00MARIE CURIEPRBB-CRG SessionsSophie DumontDept. of Bioengineering and Therapeutic Sciences, Dept. of Biochemistry and Biophysics, UCSF, San Francisco, USA"Mechanics of the kinetochore-microtubule interface: mechanisms and functions"Host: Thomas SurreyAbstract:The kinetochore links chromosomes to spindle microtubules to drive chromosome segregation at cell division. While we know nearly all mammalian kinetochore proteins, how these give rise to the kinetochore’s emergent mechanics and function remains poorly understood. First, I will discuss our work probing how kinetochores can form microtubule attachments that are at once strong yet dynamic, two seemingly opposite properties required for function. We show that one kinetochore protein complex (Astrin/SKAP) reduces friction on microtubules, effectively acting as a “lubricant”. In contrast, all previously described kinetochore proteins increase grip on microtubules. We propose that lubricating correct, bioriented attachments helps preserve them. Second, I will discuss our work probing how kinetochores can discriminate between correct and incorrect attachments. We test the long-standing model that tension serves as the stabilizing cue at correct attachments, and its implications on chromosomes of different sizes. We show that long chromosomes correct attachment errors slower than short ones due to large forces on chromosome arms that mimic correct attachment. We propose a model where increased force on long chromosomes stabilize not only correct but also incorrect attachments, delaying their biorientation and alignment. As such, long chromosomes may experience more challenges correcting errors and, as a result, higher missegregation rates.