Ana Losada Group Leader
T +34 917328000 (Ext 3470)
alosada@cnio.es

Our research focuses on a protein complex named cohesin that embraces DNA and is essential for chromosome organisation. Cohesin mediates sister chromatid cohesion and, thereby, ensures faithful DNA repair by homologous recombination and proper chromosome segregation during cell division. It also plays a major role in the spatial organisation of the genome by promoting longrange DNA looping, which in turn contributes to transcriptional regulation, organisation of DNA replication factories and locus rearrangement by recombination. Mutations in cohesin have been found in several tumour types, most prominently in bladder cancer and acute myeloid leukaemia. Mutations in cohesin and its regulatory factors are also at the origin of a group of human 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 in somatic cells. We use mouse models carrying knock out alleles of genes encoding cohesin subunit to investigate their functional specificity both at the cellular level and in the context of an organism. We also take advantage of the Xenopus egg cell-free system to explore additional aspects of cohesin regulation.

Publications

• Distinct roles of cohesin-SA1 and cohesin-SA2 in 3D chromosome organization.(2018)
  Kojic A, Cuadrado A, De Koninck M, Giménez-Llorente D, Rodríguez-Corsino M, Gómez-López G, Le Dily F, Marti-Renom MA, Losada A.
  Nat Struct Mol Biol 25, 496-504.
• Establishing and dissolving cohesion during the vertebrate cell cycle.(2018)
  Morales C, Losada A
  Curr Opin Cell Biol 52, 51-57.
• Persistent accumulation of unrepaired DNA damage in rat cortical neurons: nuclear organization and ChIP-seq analysis of damaged DNA.(2018)
  Mata-Garrido J, Tapia O, Casafont I, Berciano MT, Cuadrado A, Lafarga M.
  Acta Neuropathol Commun 6, 68-.
• The human Cranio Facial Development Protein 1 (Cfdp1) gene encodes a protein required for the maintenance of higher-order chromatin organization.(2017)
  Messina G, Atterrato MT, Prozzillo Y, Piacentini L, Losada A, Dimitri P
  Sci Rep 7, 45022-.
• Cohesin Mutations in Cancer.(2016)
  De Koninck M, Losada A
  Cold Spring Harb Perspect Med 6, a026476-.
• Sororin loads to the synaptonemal complex central region independently of meiotic cohesin complexes.(2016)
  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
  EMBO Rep 17, 695-707.
• Chromatin determinants of the inner-centromere rely on replication factors with functions that impart cohesion.(2016)
  Abe T, Kawasumi R, Arakawa H, Hori T, Shirahige K, Losada A, Fukagawa T, Branzei D
  Oncotarget 7, 67934-67947.
• Bub1 targeting to centromeres is sufficient for Sgo1 recruitment in the absence of kinetochores.(2016)
  Williams SJ, Abrieu A, Losada A
  Chromosoma 126, 279-286.
• The contribution of cohesin-SA1 to gene expression and chromatin architecture in two murine tissues.(2015)
  Cuadrado A, Remeseiro S, Graña O, Pisano, DG, Losada A
  Nucleic Acids Res 43, 3056-3067.
• The distinct functions of CENP-C and CENP-T/W in centromere propagation and function in Xenopus egg extracts.(2015)
  Krizaic I, Williams SJ, Sánchez P, Rodríguez-Corsino M, Stukenberg PT, Losada A
  Nucleus 6, 133-143.
• Cohesin in cancer: chromosome segregation and beyond.(2014)
  Losada A
  Nat Rev Cancer 14, 389-393.
• Could a patient with SMC1A duplication be classified as a human cohesinopathy?(2014)
  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
  Clin Genet 85, 446-451.
• A proteomic characterization of factors enriched at nascent DNA molecules.(2013)
  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
  Cell Reports 3, 1-12.
• Recurrent inactivation of STAG2 in bladder cancer is not associated with aneuploidy.(2013)
  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
  Nat Genet 45, 1464-1469.
• Cohesin, a chromatin engagement ring.(2013)
  Remeseiro S, Losada A
  Curr Opin Cell Biol 25, 63-71.
• Pds5B is required for cohesion establishment and Aurora B accumulation at centromeres.(2013)
  Carretero M, Ruiz-Torres M, Rodríguez-Corsino M, Barthelemy I, Losada A
  EMBO J 32, 2938-2949.
• Understanding chromatin and chromosomes: from static views to dynamic thinking.(2013)
  Haering CH, Losada A
  EMBO Rep 14, 109-111.
• Cohesin in development and disease.(2013)
  Remeseiro S, Cuadrado A, Losada A
  Development 140, 3715-3718.
• Esperanto for histones: CENP-A, not CenH3, is the centromeric histone H3 variant.(2013)
  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
  Chromosome Res 2, 101-106.
• Reduction of Nipbl impairs cohesin loading locally and affects transcription but not cohesion-dependent functions in a mouse model of Cornelia de Lange Syndrome.(2013)
  Remeseiro S, Cuadrado A, Kawauchi S, Calof AL, Lander AD, Losada A
  Biochim Biophys Acta 1832, 2097-2102.