Dr. Marion Pesenti
Project Group Leader, Mechanistic Cell Biology
Mitosis is the most spectacular event in the life of a cell. It is the process by wich a cell divides and the duplicated genetic information is equally distributed to the daughter cells. There are four main players involved in this process: 1) the replicated chromosomes; 2) the centrosomes, which act as main microtubule organizing centers in animal cells; 3) the mitotic spindles, the microtubule based structures which generate the pulling forces required for chromosome alignment and segregation; and 4) the kinetochores, which provide the platform on sister chromatids for microtubules binding. Kinetochores also recruit and control a cell cycle checkpoint, the spindle assembly checkpoint, which coordinates mitotic exit with the completion of chromosome alignment on the mitotic spindle.
With multiple copies of at least 30 structural core subunits and a myriad of regulatory subunits, kinetochores are among the largest known macromolecular machines. In the department of Mechanistic Cell Biology we try to comprehend their complex molecular organization, structure and function using a combination of in vitro techniques, including biochemical reconstitutions, structural studies and biophysical characterization, and together with sophisticated cell biology, and microscopy technologies.
We ultimately aim to unveil the organizational principles of these complex and fascinating kinetochores, essential for faithful chromosome segregation and genomic stability in cell division.
Pesenti ME, Raisch T, Conti D, Walstein K, Hoffmann I, Vogt D, Prumbaum D, Vetter IR, Raunser S, Musacchio A (2022). Structure of the human inner kinetochore CCAN complex and its significance for human centromere organization. Mol Cell
Singh P, Pesenti ME, Maffini S, Carmignani S, Hedtfeld M, Petrovic A, Srinivasamani A, Bange T, Musacchio 2020). BUB1 and CENP-U, Primed by CDK1, Are the Main PLK1 Kinetochore Receptors in Mitosis. Mol Cell
Pesenti ME, Prumbaum D, Auckland P, Smith CM, Faesen AC, Petrovic A, Erent M, Maffini S, Pentakota S, Weir JR, Lin YC, Raunser S, McAinsh AD, Musacchio A (2018). Reconstitution of a 26-Subunit Human Kinetochore Reveals Cooperative Microtubule Binding by CENP-OPQUR and NDC80. Mol Cell
Weir JR, Faesen AC, Klare K, Petrovic A, Basilico F, Fischböck J, Pentakota S, Keller J, Pesenti ME, Pan D, Vogt D, Wohlgemuth S, Herzog F, Musacchio A (2016). Insights from biochemical reconstitution into the architecture of human kinetochores. Nature 537(7619):249-253. Source
Pesenti ME, Weir JR, Musacchio A (2016). Progress in the structural and functional characterization of kinetochores. Curr Opin Struct 37:152-63. doi: 10.1016/j.sbi.2016.03.003. Source