Lecture topic: Building up from scratch the large and very complex molecular machine required for chromosome segregation
Kinetochores provide chromosomes with points of attachment to spindle microtubules during cell division, and are therefore essential for genome inheritance and the propagation of life. In addition to binding microtubules, kinetochores control mitotic surveillance mechanisms that promote chromosome bi-orientation (the error correction mechanism) and prevent premature mitotic exit in presence of incomplete or incorrect microtubule attachments (spindle assembly checkpoint, SAC). Collectively, kinetochores consist of approximately 30 core subunits in two large subcomplexes (abbreviated the CCAN and the KMN) and a plethora of regulatory subunits. They establish an internal phosphorylation gradient to sense microtubule-generated forces and to regulate the quality of kinetochore-microtubule attachment accordingly. How is all this achieved? We are trying to address this fundamental question using human kinetochores as model systems, and in vitro biochemical reconstitution as our main entry strategy, with additional important contributions from cell and structural biology.
