Description
Department for BioMedical Research (DBMR)Cells are equipped with DNA repair pathways that in conjunction with cell cycle checkpoint maintain genome integrity. Specifically, cell cycle checkpoints prevent entry into mitosis when DNA is not completely replicated DNA or when DNA lesions remain unrepaired. Preventing mitotic DNA damage is relevant because the canonical DNA repair pathways HR and NHEJ are inactivated during mitosis. In contrast to untransformed cells, cancer cells frequently enter mitosis with persistent DNA lesions, and apparently have pathways to deal with these DNA lesions. Indeed, mitotic cells appear to have dedicated pathways to process DNA damage, although the mechanistic wiring and the players involved remain largely elusive. We have recently used proteomic analyses to identify factors that respond to mitotic DNA damage. Using genetic approaches and ‘stimulated emission depletion microscopy (STED)’ microscopy approaches, we demonstrate how the TOPBP1-CIP2A complex is organized during progression through mitosis and how it recruits DNA repair factors, particularly the SMX nuclease complex in mitosis to process genomic regions of under-replicated DNA. Finally, we show how TOPBP1-CIP2A-mediated recruitment of the SMX complex determines viability in BRCA1/2 mutant cells.
| Period | 5-Feb-2025 |
|---|---|
| Held at | University of Bern, Switzerland |
| Degree of Recognition | International |