Grupo de Dinámica Cromosómica

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

Investigadores

Ana Cuadrado

Becarios Pre-Doctorales

Dácil del Pilar Alonso
Magali De Koninck
Carmen María Morales

Técnicos de Laboratorio

Daniel Giménez
Marta Renshaw
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. Germ line 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

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
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.
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.
Williams SJ, Abrieu A, Losada A (2016). Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores.. Chromosoma 126, 279-286. Publicación CNIO.
Cuadrado A, Remeseiro S, Graña O, Pisano, DG, Losada A (2015). The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues.. Nucleic Acids Res 43, 3056-3067. Publicación CNIO.
Krizaic I, Williams SJ, Sánchez P, Rodríguez-Corsino M, Stukenberg PT, Losada A (2015). The distinct functions of CENP-C and CENP-T/W in centromere propagation and function in Xenopus egg extracts.. Nucleus 6, 133-143. Publicación CNIO.
Losada A (2014). Cohesin in cancer: chromosome segregation and beyond.. Nat Rev Cancer 14, 389-393. Publicación CNIO.
Baquero-Montoya C, Gil-Rodríguez M, Teresa-Rodrigo M, Hernández-Marcos M, Bueno-Lozano G, Bueno-Martínez I, Remeseiro S, Fernández-Hernández R, Bassecourt-Serra M, Rodríguez de Alba M, Queralt E, Losada A, Puisac B, Ramos F, Pié J (2014). Could a patient with SMC1A duplication be classified as a human cohesinopathy?. Clin Genet 85, 446-451. Publicación CNIO.
López-Contreras AJ, Ruppen I, Nieto-Soler M, Murga M, Rodriguez- Acebes S, Remeseiro S, Rodrigo-Perez S, Rojas AM, Mendez J, Muñoz J, Fernandez-Capetillo O (2013). A proteomic characterization of factors enriched at nascent DNA molecules.. Cell Reports 3, 1-12. Publicación CNIO.
Balbás-Martínez C, Sagrera A, Carrillo-de-Santa-Pau E, Earl J, Márquez M, Vazquez M, Lapi E, Castro-Giner F, Beltran S, Bayés M, Carrato A, Cigudosa JC, Domínguez O, Gut M, Herranz J, Juanpere N, Kogevinas M, Langa X, López-Knowles E, Lorente JA, Lloreta J, Pisano DG, Richart L, Rico D, Salgado RN, Tardón A, Chanock S, Heath S, Valencia A, Losada A, Gut I, Malats N, Real FX (2013). Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.. Nat Genet 45, 1464-1469. Publicación CNIO.
Remeseiro S, Losada A (2013). Cohesin, a chromatin engagement ring.. Curr Opin Cell Biol 25, 63-71. Publicación CNIO.
Carretero M, Ruiz-Torres M, Rodríguez-Corsino M, Barthelemy I, Losada A (2013). Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres.. EMBO J 32, 2938-2949. Publicación CNIO.
Haering CH, Losada A (2013). Understanding chromatin and chromosomes: from static views to dynamic thinking.. EMBO Rep 14, 109-111. Publicación CNIO.
Remeseiro S, Cuadrado A, Losada A (2013). Cohesin in development and disease.. Development 140, 3715-3718. Publicación CNIO.
Earnshaw WC, Allshire RC, Black BE, Bloom K, Brinkley BR, Brown W, Cheeseman IM, Choo KH, Copenhaver GP, Deluca JG, Desai A, Diekmann S, Erhardt S, Fitzgerald-Hayes M, Foltz D, Fukagawa T, Gassmann R, Gerlich DW, Glover DM, Gorbsky GJ, Harrison SC, Heun P, Hirota T, Jansen LE, Karpen G, Kops GJ, Lampson MA, Lens SM, Losada A, Luger K, Maiato H, Maddox PS, Margolis RL, Masumoto H, McAinsh AD, Mellone BG, Meraldi P, Musacchio A, Oegema K, O'Neill RJ, Salmon ED, Scott KC, Straight AF, Stukenberg PT, Sullivan BA, Sullivan KF, Sunkel CE, Swedlow JR, Walczak CE, Warburton PE, Westermann S, Willard HF, Wordeman L, Yanagida M, Yen TJ, Yoda K, Cleveland DW (2013). Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.. Chromosome Res 2, 101-106. Publicación CNIO.
Remeseiro S, Cuadrado A, Kawauchi S, Calof AL, Lander AD, Losada A (2013). Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome.. Biochim Biophys Acta 1832, 2097-2102. Publicación CNIO.