Felipe Cortés Group Leader
T +34 000003560 (Ext 3560)
fcortes@cnio.es

DNA topoisomerases have a dual relationship with the genome. On the one hand, they are essential to solve the topological problems in the form of supercoiling, knots and tangles that are inherent to all DNA transactions. On the other hand, their intrinsic mechanism of action involves transient DNA cleavage, and can therefore result in the formation of highly cytotoxic and clastogenic DNA breaks, which not only occur accidentally during normal cellular metabolism, but also underlie the clinical efficacy of an important group of antitumour agents known as topoisomerase poisons. Imbalances in DNA topoisomerase activity can therefore compromise cell survival and genome integrity, entailing serious consequences and implications for human health, such as developmental and degenerative problems, and very importantly, neoplastic transformation processes and their subsequent response to treatment.

Our laboratory is interested in understanding how DNA topoisomerase activity is regulated to integrate different aspects of genome dynamics, from its 3D organisation and expression, to its duplication, condensation and segregation, 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. In order to do so, we undertake a comprehensive approach, combining detailed molecular, cellular and genome wide analyses with more physiological studies in mouse models, with a final aim at exploiting our discoveries in cancer prevention and treatment.

Publications

• Pintado-Berninches L, Fernandez-Varas B, Benitez-Buelga C, Manguan-Garcia C, Serrano-Benitez A, Iarriccio L, Carrillo J, Guenechea G, Egusquiaguirre SP, Pedraz JL, Hernández RM, Igartua M, Arias-Salgado EG, Cortés-Ledesma F, Sastre L, Perona R (2019). GSE4 peptide suppresses oxidative and telomere deficiencies in ataxia telangiectasia patient cells. Cell Death Differ 26, 1998-2014. CNIO Publication.
• Schellenberg MJ, Lieberman JA, Herrero-Ruiz A, Butler LR, Williams JG, Muñoz-Cabello AM, Mueller GA, London RE, Cortés-Ledesma F, Williams RS (2017). ZATT (ZNF451)-mediated resolution of topoisomerase 2 DNA-protein cross-links.. Science 357, 1412-1416. Publication in other institutions.
• Feng W, Kawauchi D, Körkel-Qu H, Deng H, Serger E, Sieber L, Lieberman JA, Jimeno-González S, Lambo S, Hanna BS, Harim Y, Jansen M, Neuerburg A, Friesen O, Zuckermann M, Rajendran V, Gronych J, Ayrault O, Korshunov A, Jones DT, Kool M, Northcott PA, Lichter P, Cortés-Ledesma F, Pfister SM, Liu HK (2017). Chd7 is indispensable for mammalian brain development through activation of a neuronal differentiation programme. Nat Commun 8, 14758. Publication in other institutions.
• Sastre-Moreno G, Pryor JM, Moreno-Oñate M, Herrero-Ruiz AM, Cortés-Ledesma F, Blanco L, Ramsden DA, Ruiz JF (2017). Regulation of human pol? by ATM-mediated phosphorylation during non-homologous end joining.. Dna Repair 51, 31-45. Publication in other institutions.
• Caron P, Choudjaye J, Clouaire T, Bugler B, Daburon V, Aguirrebengoa M, Mangeat T, Iacovoni JS, Álvarez-Quilón A, Cortés-Ledesma F, Legube G (2015). Non-redundant Functions of ATM and DNA-PKcs in Response to DNA Double-Strand Breaks.. Cell Reports 13, 1598-1609. Publication in other institutions.