Our Group studies the fundamental mechanisms of DNA replication and how the replicative process adapts to cell type-specific transcriptional programmes and chromatin organisation. We also investigate the cellular responses to replication stress (RS), a phenomenon caused by endogenous or exogenous factors that slow down DNA replication forks and may result in DNA damage and genomic instability. Our long-term goal is to develop strategies to minimise RS in normal cells and enhance it in cancer cells to increase their vulnerability. In 2023, we addressed the molecular changes that underlie the rewiring of DNA replication during pluripotency transitions in mouse embryonic stem cells. We also described how regulation of replication origin activity influences the acquisition of chemotherapy resistance in tumour cells undergoing epithelial-to-mesenchymal transition. Finally, we showed how DNA replication is blocked by a new combination therapy for diffuse large B cell lymphoma.
Investigadores Científicos
- Estrella Guarino
- Susana Llanos
- Sara Rodríguez
Becarios Post-doctorales
- Sergio Muñoz
Becarios Pre-Doctorales
- Miguel Curto
- Roberto Masdemont
- Sergi Roig
Publicaciones
- (2024). RAD51 restricts DNA over-replication from re-activated origins. EMBO J 43, 1043-1064. Publicación CNIO.
- (2024). SIN3A histone deacetylase action counteracts MUS81 to promote stalled fork stability. Cell Reports 43, 113778. 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). Interference of small compounds and Mg2+ with dsRNA-binding fluorophores compromises the identification of SARS-CoV-2 RdRp inhibitors. Sci Rep 14, 28250. Publicación CNIO.
- (2024). PARP1, DIDO3, and DHX9 Proteins Mutually Interact in Mouse Fibroblasts, with Effects on DNA Replication Dynamics, Senescence, and Oncogenic Transformation. Cells 13, 159. Publicación CNIO.
- (2023). RHOJ controls EMT-associated resistance to chemotherapy. Nature 616, 168-175. Publicación CNIO.
- (2023). miR-28-based combination therapy impairs aggressive B cell lymphoma growth by rewiring DNA replication. Cell Death Dis 14, 687. Publicación CNIO.
- (2022). Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming. Mol Cell 38, 4176-4188. Publicación CNIO.
- (2022). 3D chromatin connectivity underlies replication origin efficiency in mouse embryonic stem cells. Nucleic Acids Res 50, 12149-12165. Publicación CNIO.
Open Access - (2022). A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions. Cell Death Differ 29, 2347-2361. Publicación CNIO.
- (2022). Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage. Cell Reports 40, 111375. Publicación CNIO.
- (2021). Motif WFYY of human PrimPol is crucial to stabilize the incoming 3′-nucleotide during replication fork restart. Nucleic Acids Res 49, 8199-8213. Publicación CNIO. Open Access
- (2021). PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks. EMBO J 40, e106355. Publicación CNIO.
- (2020). PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells.. Mol Cell 77, 461-474. Publicación CNIO.
- (2020). PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts. Nat Commun 11, 5863. Publicación CNIO. Open Access
- (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