DNA topoisomerases have a dual relationship with the genome. They are essential to solve supercoiling and other topological problems inherent to all DNA transactions, but their intrinsic mechanism of action can result in the formation of DNA breaks, either accidentally during normal cellular metabolism or upon chemotherapy treatment with the so-called topoisomerase poisons. Imbalances in DNA topoisomerase activity can therefore compromise cell survival and genome integrity, entailing serious consequences for human health, such as developmental and degenerative problems and, very importantly, neoplastic transformation processes and their subsequent response to treatment.
We are interested in understanding how DNA topoisomerase activity is regulated to integrate different aspects of genome dynamics, how an imbalance in these processes can lead to the appearance of pathological DNA breaks, and how cells specifically respond to these lesions to maintain genome stability.
Publications
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Olivieri M, Cho T, Álvarez-Quilón A, Li K, Schellenberg MJ, Zimmermann M, Hustedt N, Rossi SE, Adam S, Melo H, Heijink AM, Sastre-Moreno G, Moatti N, Szilard RK, McEwan A, Ling AK, Serrano-Benitez A, Ubhi T, Feng S, Pawling J, Delgado-Sainz I, Ferguson MW, Dennis JW, Brown GW, Cortés-Ledesma F, Williams RS, Martin A, Xu D, Durocher D (2020).A genetic map of the response to DNA damage in human cells. Cell 182, 481-496. CNIO Publication.
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Open Access