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Friday, September 15th, 2023
Centre de recherche - Orsay - Amphithéâtre du Bâtiment 111

Exploiting self-inflicted DNA breaks to evade growth limits imposed by genotoxic stress

I will present two discoveries from my team dealing with precision medicine approaches and possibilities. The first part deals with widely used genotoxic cancer therapy, such as irradiation. These modalities operate through extensive induction of DNA breaks, yet cancer cells frequently display resistance to such interventions. Intriguingly, studies following the dynamics of radiation-induced DNA lesions have identified a temporally distinct and unexplained secondary wave of DNA breaks. Here, I will present our findings on a new pathway that allows tolerance to genotoxic stress. We uncovered that cancer cells actively and reversibly elevate levels of DNA breaks, a mechanism that acts to strengthen the G2/M cell cycle checkpoint thereby limiting premature re-entry into the cell cycle. I will explain the mechanisms underlying this response, which is distinct for cancer cells. Collectively, our findings highlight an unanticipated discovery in cancer biology, demonstrating that tumor cells deploy regulated DNA breaks as a mechanism to delimit the detrimental effects of exogenous DNA double-strand breakage and ensure survival. Finally, in the second part of my presentation I will outline our new approach to determine the phenotypic impact of genetic variants including their impact on drug responses. We call our approach CRISPR-Select, which allows for precise, quantitative, and rapid analysis without the need for generation of clones or selection. It provides unique opportunities for example to identify cancer-causing or drug-response predicting mutations.   


Claus Storgaard Sorensen, Ph.D.

Associate Professor, Group leader - University of Copenhagen

Invited by

Stephan Vagner
Intégrité du génome, ARN et Cancer (UMR3348)

Institut Curie