Grupo de Dinámica Cromosómica

Ana Losada Jefe de Grupo
T +34 917328000 (Ext 3470)
alosada@cnio.es

Investigadores

Ana Cuadrado

Becarios Post-doctorales

María José Andreu

Becarios Pre-Doctorales

Dácil del Pilar Alonso
Inmaculada Sanclemente
María Solé

Técnicos de Laboratorio

Daniel Giménez
Miriam Rodríguez

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.

Publicaciones

Andreu MJ, Alvarez-Franco A, Portela M, Giménez-Llorente D, Cuadrado A, Badia-Careaga C, Tiana M, Losada A, Manzanares M (2021). Establishment of 3D chromatin structure after fertilization and the metabolic switch at the morula-to-blastocyst transition require CTCF.. bioRxiv (in press). Publicación CNIO.
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. Publicación CNIO.
Garcia P, Fernandez-Hernandez R, Cuadrado A, Coca I, Gomez A, Maqueda M, Latorre-Pellicer A, Puisac B, Ramos FJ, Sandoval J, Esteller M, Mosquera JL, Rodriguez J, Pié J, Losada A, Queralt E (2021). Disruption of NIPBL/Scc2 in Cornelia de Lange Syndrome provokes cohesin genome-wide redistribution with an impact in the transcriptome. Nat Commun 12, 4551. Publicación CNIO. Open Access
Morales C, Ruiz-Torres M, Rodríguez-Acebes S, Lafarga V, Rodríguez-Corsino M, Megías D, Cisneros DA, Peters JM, Méndez J, Losada A (2020). PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. J Biol Chem 295, 146-157. Publicación CNIO. Open Access
Cuadrado A, Losada A (2020). Specialized functions of cohesins STAG1 and STAG2 in 3D genome architecture.. Curr Opin Genet Dev 61, 9-16. Publicación CNIO.
De Koninck M, Lapi E, Badía-Careaga C, Cossío I, Giménez-Llorente D, Rodríguez-Corsino M, Andrada E, Hidalgo A, Manzanares M, Real FX, Losada A (2020). Essential Roles of Cohesin STAG2 in Mouse Embryonic Development and Adult Tissue Homeostasis.. Cell Reports 32, 108014. Publicación CNIO. Open Access
Viera A, Berenguer I, Ruiz-Torres M, Gómez R, Guajardo A, Barbero JL, Losada A, Suja JA (2020). PDS5 proteins regulate the length of axial elements and telomere integrity during male mouse meiosis. EMBO Rep 21, e49273. Publicación CNIO.
Cuadrado A, Giménez-Llorente D, Kojic A, Rodríguez-Corsino M, Cuartero Y, Martin-Serrano G, Gómez-López G, Marti-Renom MA, Losada A (2019). Specific Contributions of Cohesin-SA1 and Cohesin-SA2 to TADs and Polycomb Domains in Embryonic Stem Cells.. Cell Reports 27, 3500-3510. Publicación CNIO. Open Access
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). Publicación CNIO.
Kojic A, Cuadrado A, De Koninck M, Giménez-Llorente D, Rodríguez-Corsino M, Gómez-López G, Le Dily F, Marti-Renom MA, Losada A (2018). Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization. Nat Struct Mol Biol 25, 496-504. Publicación CNIO.
Morales C, Losada A (2018). Establishing and dissolving cohesion during the vertebrate cell cycle. Curr Opin Cell Biol 52, 51-57. Publicación CNIO.
Mata-Garrido J, Tapia O, Casafont I, Berciano MT, Cuadrado A, Lafarga M (2018). Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA. Acta Neuropathol Commun 6, 68. Publicación CNIO. Open Access
Messina G, Atterrato MT, Prozzillo Y, Piacentini L, Losada A, Dimitri P (2017). The human Cranio Facial Development Protein 1 (Cfdp1) gene encodes a protein required for the maintenance of higher-order chromatin organization. Sci Rep 7, 45022. Publicación CNIO.
Williams SJ, Abrieu A, Losada A (2017). Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores. Chromosoma 126, 279-286. Publicación CNIO.
De Koninck M, Losada A (2016). Cohesin Mutations in Cancer.. Cold Spring Harb Perspect Med 6, a026476. Publicación CNIO.
Gómez R, Felipe-Medina N, Ruiz-Torres M, Berenguer I, Viera A, Pérez S, Barbero JL, LLano E, Fukuda T, Alsheimer M, Pendás AM, Losada A, Suja A (2016). Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes.. EMBO Rep 17, 695-707. Publicación CNIO.
Abe T, Kawasumi R, Arakawa H, Hori T, Shirahige K, Losada A, Fukagawa T, Branzei D (2016). Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.. Oncotarget 7, 67934-67947. Publicación CNIO.