- Susana Llanos
- Sara Rodríguez
- Estrella Guarino
- Sergio Muñoz
- Elena Blanco
- Patricia Ubieto
Our laboratory studies the process of genome duplication, which is responsible for many of the mutations and genomic alterations found in human cancer. While the protein machinery responsible for DNA replication is normally very accurate, it becomes error-prone when the DNA displays chemical alterations caused by endogenous reactive species, external drugs or ionising radiation. We are interested in the phenomenon of replicative tolerance, i.e. the mechanisms that allow the progression of the ‘replisome’ proteins through damaged DNA, a step that normally precedes the activation of specific DNA repair pathways. In 2019, we focused on two major areas: (1) studying the efficiency of replication origins in response to replication stress in pluripotent cells, in the context of their three-dimensional positions in the nuclear chromatin; and (2) evaluating the function of DNA primase PrimPol in the tolerance of cytotoxic DNA lesions in normal and cancer cells with different genetic backgrounds.
- (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.
- (2019). Identification and characterization of Cardiac Glycosides as senolytic compounds.. Nat Commun 10, 4731. CNIO Publication. Open Access
- (2019). Lysosomal trapping of palbociclib and its functional implications. Oncogene 38, 3886-3902. CNIO Publication.
- (2019). TIAR marks nuclear G2/M transition granules and restricts CDK1 activity under replication stress. EMBO Rep 20, e46224. CNIO Publication.
- (2019). A cancer-associated point mutation disables the steric gate of human PrimPol. Sci Rep 9, 1121. 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). 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). In Vivo DNA Re-replication Elicits Lethal Tissue Dysplasias. Cell Reports 19, 928-938. 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). DNA replication stress: from molecular mechanisms to human disease.. Chromosoma 126, 1-15. CNIO Publication.
- (2016). USP37 deubiquitinates Cdt1 and contributes to regulate DNA replication. Mol Oncol 10, 1196-1206. CNIO Publication. Open Access
- (2016). DNA replication stress: from molecular mechanisms to human disease.. Chromosoma (in press). CNIO Publication.
- (2016). Molecular architecture of the recombinant human MCM2-7 helicase in complex with nucleotides and DNA.. Cell Cycle 15, 2431-2440. CNIO Publication.
- (2016). USP7 is a SUMO deubiquitinase essential for DNA replication.. Nat Struct Mol Biol 23, 270-277. CNIO Publication.
- (2016). POLD3 Is Haploinsufficient for DNA Replication in Mice. Mol Cell 63, 877-883. CNIO Publication.
- (2016). A short G1 phase imposes constitutive replication stress and fork remodelling in mouse embryonic stem cells. Nat Commun 7, 10660. CNIO Publication. Open Access