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, DNA replication and recombination. Two variant cohesin complexes, carrying either the STAG1 or the STAG2 subunit, are present in all somatic vertebrate cells. While cells require a single complex for viability, both are necessary to fulfill embryonic development. Mutations in cohesin genes, most prominently in STAG2, have been found in several tumour types, including bladder cancer, Ewing sarcoma, and acute myeloid leukaemia. Germline mutations in cohesin and its regulatory factors are also at the origin of developmental syndromes collectively known as cohesinopathies, such as Cornelia de Lange Syndrome (CdLS). Our goal is to understand how cohesin works, how it is regulated, and how its dysfunction contributes to cancer and other human diseases.
Investigadores Científicos
- Ana Cuadrado
Becarios Pre-Doctorales
- Sofía Cecilia García
- Ana Rita Marques
- Inmaculada Sanclemente
- María Solé
- Francisco Javier Valero
Técnicos de Laboratorio
- Daniel Giménez
- Miriam Rodríguez
Publicaciones
- (2025). Cohesin in 3D: development, differentiation, and disease. Genes Dev 39, 679-696. Publicación CNIO.
- (2024). A rewiring of DNA replication mediated by MRE11 exonuclease underlies primed-to-naive cell de-differentiation. Cell Reports 43, 114024. Publicación CNIO.
- (2024). STAG2 loss in Ewing sarcoma alters enhancer-promoter contacts dependent and independent of EWS::FLI1.. EMBO Rep 25, 5537-5560. Publicación CNIO.
Open Access - (2024). miR-203 controls developmental timing and early fate restriction during preimplantation embryogenesis.. BioRxiv (in press). Publicación CNIO. More Info
- (2024). A comprehensive genetic catalog of human double-strand break repair.. BioRxiv (in press). Publicación CNIO. More Info
- (2023). NIPBL and cohesin: new take on a classic tale. Trends Cell Biol 33, 860-871. Publicación CNIO. Open Access
- (2023). Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2.. Nat Commun 14, 1326. Publicación CNIO. Open Access
- (2023). Protocol to analyze chromatin-bound proteins through the cell cycle using Chromoflow flow cytometry. Star Protocols 4, 102568. Publicación CNIO.
- (2023). A protocol to study three-dimensional genome structure in individual mutant preimplantation mouse embryos.. Star Protoc 4, 102267. Publicación CNIO.
- (2022). Mammalian CDC14 phosphatases control exit from stemness in pluripotent cells.. EMBO J 42, e111251. Publicación CNIO.
- (2022). Establishment of 3D chromatin structure after fertilization and the metabolic switch at the morula-to-blastocyst transition require CTCF.. Cell Reports 41, 111501. Publicación CNIO.
- (2022). Contribution of variant subunits and associated factors to genome-wide distribution and dynamics of cohesin.. Epigenetics & Chromatin 15, 37. Publicación CNIO. Open Access
- (2022). Different NIPBL requirements of cohesin-STAG1 and cohesin-STAG2. bioRxiv (in press). Publicación CNIO. Open Access
- (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
- (2021). Regulatory CDH4 genetic variants associate with risk to develop capecitabine-induced hand-foot syndrome.. Clin Pharmacol Ther 109, 462-470. Publicación CNIO.
- (2020). Essential Roles of Cohesin STAG2 in Mouse Embryonic Development and Adult Tissue Homeostasis.. Cell Reports 32, 108014. Publicación CNIO. Open Access
- (2020). PDS5 proteins regulate the length of axial elements and telomere integrity during male mouse meiosis. EMBO Rep 21, e49273. Publicación CNIO. Open Access
- (2020). Specialized functions of cohesins STAG1 and STAG2 in 3D genome architecture.. Curr Opin Genet Dev 61, 9-16. Publicación CNIO.
- (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