Topology and DNA breaks Group

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

Staff Scientists

Israel Salguero

Post-Doctoral Fellows

Jonathan Barroso
Laura García

Graduate Students

Alicia Avis
Ernesto López
María del Mar Martínez

Technicians

Marta Muñoz
José Terrón

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

Rodriguez-Cortez VC, Navarrete-Meneses MP, Molina O, Velasco-Hernandez T, Gonzalez J, Romecin P, Gutierrez-Aguera F, Roca-Ho H, Vinyoles M, Kowarz E, Marin P, Rodriguez-Perales S, Gomez-Marin C, Perez-Vera P, Cortes-Ledesma F, Bigas A, Terron A, Bueno C, Menendez P. (2022). The insecticides permethrin and chlorpyrifos show limited genotoxicity and no leukemogenic potential in human and murine hematopoietic stem progenitor cells. Haematologica 107, 544-549. CNIO Publication.
Rodriguez-Cortez VC, Navarrete-Meneses MP, Molina O, Velasco-Hernandez T, Gonzalez J, Romecin P, Gutierrez-Aguera F, Roca-Ho H, Vinyoles M, Kowarz E, Marin P, Rodriguez-Perales S, Gomez-Marin C, Perez-Vera P, Cortes-Ledesma F, Bigas A, Terron A, Bueno C, Menendez P. (2022). The insecticides permethrin and chlorpyriphos show limited genotoxicity and no leukemogenic potential in human and murine hematopoietic stem progenitor cells 2021. Haematologica 107, 544-549. CNIO Publication.
Herrero-Ruiz A, Martínez-García PM, Terrón-Bautista J, Millán-Zambrano G, Lieberman JA, Jimeno-González S, Cortés-Ledesma F (2021). Topoisomerase IIa represses transcription by enforcing promoter-proximal pausing. Cell Reports 35, 108977. CNIO Publication.
Martínez-García PM, García-Torres M, Divina F, Terrón-Bautista J, Delgado-Sainz I, Gómez-Vela F, Cortés-Ledesma F (2021). Genome-wide prediction of topoisomerase IIß binding by architectural factors and chromatin accessibility. PLoS Comput Biol 17, e1007814. CNIO Publication.
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.
Schellenberg MJ, Appel CD, Riccio AA, Butler LR, Krahn JM, Liebermann JA, Cortés-Ledesma F, Williams RS (2020). Ubiquitin Stimulated Reversal of Topoisomerase 2 DNA-protein Crosslinks by TDP2. Nucleic Acids Res 48, 6310-6325. CNIO Publication. Open Access
Álvarez-Quilón A, Terrón-Bautista J, Delgado-Sainz I, Serrano-Benítez A, Romero-Granados R, Martínez-García PM, Jimeno-González S, Bernal-Lozano C, Quintero C, García-Quintanilla L, Cortés-Ledesma F (2020). Endogenous topoisomerase II-mediated DNA breaks drive thymic cancer predisposition linked to ATM deficiency. Nat Commun 11, 910. CNIO Publication. Open Access
Moreno-Oñate M, Herrero-Ruiz AM, García-Dominguez M, Cortés-Ledesma F, Ruiz JF (2020). RanBP2-Mediated SUMOylation Promotes Human DNA Polymerase Lambda Nuclear Localization and DNA Repair. J Mol Biol 432, 3965-3979. CNIO Publication.
Al Mahmud MR, Ishii K, Bernal-Lozano C, Delgado-Sainz I, Toi M, Akamatsu S, Fukumoto M, Watanabe M, Takeda S, Cortés-Ledesma F, Sasanuma H (2020). TDP2 suppresses genomic instability induced by androgens in the epithelial cells of prostate glands. Genes Cells 25, 450-465. CNIO Publication.
Serrano-Benítez A, Cortés-Ledesma F, Ruiz JF (2020). An end to a means”: how DNA-end structure shapes the double-strand break repair process”. Front Mol Biosci 6, 153. CNIO Publication.
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.