DNA replication is an essential feature of life but it entails molecular risks ranging from the introduction of mutations to the generation of breaks and chromosomal re-arrangements that promote tumorigenesis. “Replicative stress”, defined as the temporary difficulty of replisome proteins to make a copy of the original DNA, is exacerbated by environmental agents that modify the DNA chemical structure, including UV light, ionising radiation, chemicals in tobacco, and other pollutants. The efficacy of cisplatin, mitomycin C, and other chemotherapy drugs actually relies on the extensive introduction of DNA lesions that cannot be replicated or repaired. In recent years we have focused on the cellular responses to DNA lesions induced by chemotherapy, such as intra-strand and inter-strand crosslinks. In 2021 we continued to investigate the fundamental mechanisms that govern DNA replication in normal and cancer cells, and completed 2 studies about the “re-priming” mechanism activated in response to many DNA lesions.
Staff Scientists
- Susana Llanos
- Sara Rodríguez
Post-Doctoral Fellows
- Estrella Guarino
- Sergio Muñoz
Graduate Students
- Elena Blanco
- Roberto Masdemont
- Sergi Roig
- Patricia Ubieto
Publications
- (2022). Stress-triggered hematopoietic stem cell proliferation relies on PrimPol-mediated repriming. Mol Cell (in press). CNIO Publication.
- (2022). A truncating variant of RAD51B associated with primary ovarian insufficiency provides insights into its meiotic and somatic functions. Cell Death Differ (in press). CNIO Publication.
- (2022). Regulation of Claspin by the p38 stress-activated protein kinase protects cells from DNA damage. Cell Reports 40, 111375. CNIO Publication.
- (2021). Motif WFYY of human PrimPol is crucial to stabilize the incoming 3′-nucleotide during replication fork restart. Nucleic Acids Res 49, 8199-8213. CNIO Publication.
Open Access - (2021). PrimPol-mediated repriming facilitates replication traverse of DNA interstrand crosslinks. EMBO J 40, e106355. CNIO Publication.
- (2020). PRIMPOL-Mediated Adaptive Response Suppresses Replication Fork Reversal in BRCA-Deficient Cells.. Mol Cell 77, 461-474. CNIO Publication.
- (2020). PrimPol-dependent single-stranded gap formation mediates homologous recombination at bulky DNA adducts. Nat Commun 11, 5863. CNIO Publication. Open Access
- (2020). PDS5 proteins are required for proper cohesin dynamics and participate in replication fork protection. J Biol Chem 295, 146-157. CNIO Publication. Open Access
- (2019). TIAR controls mitotic entry, maintains genome stability and retains CDK1 in checkpoint bodies.. EMBO Rep 20, pii: e46224. CNIO Publication.
- (2019). Identification and characterization of Cardiac Glycosides as senolytic compounds.. Nat Commun 10, 4731. CNIO Publication. Open Access
- (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep 20, e46224. CNIO Publication.
- (2019). Lysosomal trapping of palbociclib and its functional implications. Oncogene 38, 3886-3902. CNIO Publication.
- (2019). A cancer-associated point mutation disables the steric gate of human PrimPol. Sci Rep 9, 1121. CNIO Publication. Open Access
- (2019). Three-dimensional connectivity and chromatin environment mediate the activation efficiency of mammalian DNA replication origins.. bioRxiv (in press). CNIO Publication.
- (2018). Functional interplay between c-Myc and Max in B lymphocyte differentiation. EMBO Rep 19, e45770. CNIO Publication.
- (2018). Uncoupling fork speed and origin activity to identify the primary cause of replicative stress phenotypes. J Biol Chem 293, 12855-12861. CNIO Publication.
- (2017). Shortage of dNTPs underlies altered replication dynamics and DNA breakage in the absence of the APC/C cofactor Cdh1. Oncogene 36, 5808-5818. CNIO Publication.
- (2017). In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias. Cell Reports 19, 928-938. CNIO Publication.
- (2017). DNA replication stress: from molecular mechanisms to human disease. Chromosoma 126, 1-15. CNIO Publication.
