Our research focuses on a protein complex named cohesin that embraces DNA to mediate sister chromatid cohesion, a process essential for chromosome segregation and faithful DNA repair by homologous recombination. Cohesin also plays a major role in the spatial organisation of the genome by promoting long-range DNA looping, which in turn contributes to transcriptional regulation. Mutations in cohesin have been found in several tumour types, most prominently in bladder cancer, Ewing sarcoma and acute myeloid leukaemia. Germline mutations in cohesin and its regulatory factors are also at the origin of human developmental syndromes collectively known as cohesinopathies.
Our goal is to understand how cohesin works, how it is regulated, and how its dysfunction contributes to cancer and other human diseases. In particular, we are intrigued by the existence of different versions of the cohesin complex. We use human cells and mouse models carrying knock out alleles of genes encoding variant cohesin subunits to investigate their functional specificity.
Publications
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Villarroya-Beltri C, Martins AFB, García A, Giménez D, Zarzuela E, Novo M, Del Álamo C, González-Martínez J, Bonel-Pérez GC, Díaz I, Guillamot M, Chiesa M, Losada A, Graña-Castro O, Rovira M, Muñoz J, Salazar-Roa M, Malumbres M. (2022).Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells.. EMBO J 42, e111251. CNIO Publication.
Ruiz-Pinto S, Pita G, Martín M, Nunez-Torres R, Cuadrado A, Shahbazi MN, Caronia D, Kojic A, Moreno LT, de la Torre-Montero JC, Lozano M, López-Fernández LA, Ribelles N, García-Saenz JA, Alba E, Milne RL, Losada A, Pérez-Moreno M, Benítez J, González-Neira A (2021).Regulatory CDH4 genetic variants associate with risk to develop capecitabine-induced hand-foot syndrome.. Clin Pharmacol Ther 109, 462-470. CNIO Publication.
De Koninck M, Lapi E, Badia-Careaga C, Cossio I, Giménez-Llorente D, Rodríguez-Corsino M, Andrada E, Hidalgo A, Manzanares M, Real FX, Losada (2019).STAG2 cohesin is essential for heart morphogenesis.. BioRivx (in press). CNIO Publication.
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Open Access