A5083487166- DNA Repair Mechanisms
- Cancer-related Molecular Pathways
- Microtubule and mitosis dynamics
- CRISPR and Genetic Engineering
- Phytochemical Studies and Bioactivities
- Genomics and Chromatin Dynamics
- Ubiquitin and proteasome pathways
- Phytochemistry and Bioactive Compounds
- Natural product bioactivities and synthesis
- Mitochondrial Function and Pathology
- Carcinogens and Genotoxicity Assessment
- Radical Photochemical Reactions
- Marine Toxins and Detection Methods
- Marine Sponges and Natural Products
- PARP inhibition in cancer therapy
- Carbohydrate Chemistry and Synthesis
- Steroid Chemistry and Biochemistry
- Oxidative Organic Chemistry Reactions
- Bacteriophages and microbial interactions
- Chemical Reaction Mechanisms
- Cell death mechanisms and regulation
- Synthetic Organic Chemistry Methods
- Organic Chemistry Cycloaddition Reactions
- SARS-CoV-2 and COVID-19 Research
- Sperm and Testicular Function
Universidad de La Laguna
2008-2025
Hospital Universitario de Canarias
2016-2025
Universidad Fernando Pessoa Canarias
2019-2025
Fundación Canaria de Investigación Sanitaria
2023-2024
Cornell University
2023
Unidad de Investigación en cuidados y servicios de salud (Investén-isciii)
2013-2014
Technical University of Darmstadt
2013
Universidad Europea de Canarias
2013
Consejo Superior de Investigaciones Científicas
1994-2007
Instituto de Salud Carlos III
2006
The cytotoxicity of DNA-protein crosslinks (DPCs) is largely ascribed to their ability block the progression DNA replication. DPCs frequently occur in cells, either as a consequence metabolism or exogenous agents, but mechanism DPC repair not completely understood. Here, we characterize SPRTN specialized DNA-dependent and replication-coupled metalloprotease for repair. cleaves various binding substrates during S-phase thus protects proliferative cells from toxicity. Ruijs-Aalfs syndrome...
Correct replication of the genome and protection its integrity are essential for cell survival. In a high-throughput screen studying H2AX phosphorylation, we identified Wee1 as regulator genomic stability. down-regulation not only induced phosphorylation but also triggered general deoxyribonucleic acid (DNA) damage response (DDR) caused block in DNA replication, resulting accumulation cells S phase. Wee1-deficient showed decrease fork speed, demonstrating involvement replication. Inhibiting...
The forkhead transcription factor FOXM1 has a key role in DNA damage response, and its deregulated overexpression is associated with genotoxic drug resistance breast cancer. However, little known about the posttranslational mechanisms by which expression regulated agents how they are resistant cells. Initial co-immunoprecipitation studies verified previous proteomic analysis finding that OTUB1 novel FOXM1-interacting protein. Western blot showed both reduced upon agent treatment MCF-7 cells,...
FOXM1 is implicated in genotoxic drug resistance but its mechanism of action remains elusive. We show here that FOXM1-depletion can sensitize breast cancer cells and mouse embryonic fibroblasts (MEFs) into entering epirubicin-induced senescence, with the loss long-term cell proliferation ability, accumulation γH2AX foci, induction senescence-associated β-galactosidase activity morphology. Conversely, reconstitution FOXM1-deficient MEFs alleviates foci. also demonstrate regulates NBS1 at...
In G2 phase cells, DNA double-strand break repair switches from non-homologous end-joining to homologous recombination.This switch demands the promotion of resection.We examine changes in 53BP1 and RAP80 ionizing radiation induced foci (IRIF) phase, as these are factors that restrict observed a 2-fold increase volume by 8 h, which is not seen G1 cells.Additionally, an IRIF core devoid arises where RPA form, with BRCA1 forming between replication protein A (RPA).Ubiquitin chains assessed...
DNA damaging agents cause a variety of lesions, which double-strand breaks (DSBs) are the most genotoxic. Unbiased approaches aimed at investigating relationship between number DSBs and outcome damage response have been challenging due to random nature in is induced by classical agents. Here, we describe CRISPR/Cas9-based system that permits us efficiently introduce defined sites genome. Using this system, show guide RNA targeting only single site human genome can trigger checkpoint potent...
Abstract Eukaryotic topoisomerase 1 (TOP1) regulates DNA topology to ensure efficient replication and transcription. TOP1 is also a major driver of endogenous genome instability, particularly when its catalytic intermediate—a covalent TOP1-DNA adduct known as cleavage complex (TOP1cc)—is stabilised. TOP1ccs are highly cytotoxic failure resolve them underlies the pathology neurological disorders but exploited in cancer therapy where target widely used frontline anti-cancer drugs. A critical...
In order to control the COVID-19 pandemic caused by SARS-CoV-2 infection, serious progress has been made identify infected patients and detect with a positive immune response against virus. Currently, attempts generate vaccine coronavirus are ongoing. To understand immunoreactivity, we compared IgG antibody in versus dot blot using recombinant viral particle proteins: N (Nucleocapsid), M (Membrane) S (Spike). addition, used different protein fragments of map epitopes. Most presented specific...
Rothmund-Thomson syndrome (RTS) is a human genetic disorder characterized by genome instability, cancer susceptibility and premature aging. The gene defective in subset of RTS cases, RECQL4, encodes member the RecQ family DNA helicases. To better define function RECQL4 protein, we have determined its subcellular localization. We raised antibodies against N- C-terminal parts could show that various cells endogenous forms discrete nuclear foci colocalize with promyelotic leukaemia protein...
Simian virus 40 (SV40) large T antigen (LT) is a multifunctional protein that important for viral replication and oncogenic transformation. Previously, infection of monkey or human cells with SV40 was shown to lead the induction DNA damage response signaling, which required efficient replication. However, it not clear if LT sufficient induce and, so, what genetic requirements functional consequences might be. Here, we show expression alone, without origin, can key markers including...
Polo-like kinase-1 (Plk1) is required for proper cell division. Activation of Plk1 requires phosphorylation on a conserved threonine in the T-loop kinase domain (T210). first phosphorylated T210 G2 phase by Aurora-A, concert with its cofactor Bora. However, Bora was shown to be degraded prior entry into mitosis, and it currently unclear how activity sustained mitosis. Here we show that Bora/Aurora-A complex remains major activator We small amount Aurora-A sufficient phosphorylate activate In...
Although DNA non-homologous end-joining repairs most double-strand breaks (DSBs) in G2 phase, late repairing DSBs undergo resection and repair by homologous recombination (HR). Based on parallels to the situation G1 cells, previous work has suggested that HR predominantly localize regions of heterochromatin (HC). By using H3K9me3 H4K20me3 identify HC regions, we substantiate extend evidence, suggesting HC-DSBs HR. Next, examine roles for 53BP1 BRCA1 this process. Previous studies have shown...
Abstract Human CtIP is a decisive factor in DNA double-strand break repair pathway choice by enabling DNA-end resection, the first step that differentiates homologous recombination (HR) from non-homologous end-joining (NHEJ). To coordinate appropriate and timely execution of function tightly controlled multiple protein–protein interactions post-translational modifications. Here, we identify Cullin3 E3 ligase substrate adaptor Kelch-like protein 15 (KLHL15) as new interaction partner show...
Article15 October 2019Open Access Source DataTransparent process The p97–Ataxin 3 complex regulates homeostasis of the DNA damage response E3 ubiquitin ligase RNF8 Abhay Narayan Singh Department Oncology, Cancer Research UK/Medical Council Oxford Institute for Radiation University Oxford, UK Search more papers by this author Judith Oehler Ignacio Torrecilla Susan Kilgas Shudong Li Bruno Vaz Claire Guérillon Novo Nordisk Foundation Center Protein Research, Copenhagen, Denmark John Fielden...
Preventing or delaying progress through the cell cycle in response to DNA damage is crucial for eukaryotic cells allow be repaired and not incorporated irrevocably into daughter cells. Several genes involved this process have been discovered fission budding yeast. Here, we report identification of human mouse homologs Schizosaccharomyces pombe checkpoint control gene rad1(+) its Saccharomyces cerevisiae homolog RAD17. The HRAD1 located on chromosome 5p13 most homologous S. rad1(+). This...
The mitotic spindle checkpoint protein Bub1 has been found to be mutated at low frequency in certain human cancers characterized by aneuploidy. Simian virus 40 large T antigen efficiently immortalizes rodent cells and occasionally transforms them tumorigenicity. can also cause genomic instability, inducing chromosomal aberrations Here, we report an interaction between antigen. coimmunoprecipitates with endogenous Bub3, another component of the complex. Genetic analysis demonstrates that is...
The mammalian ortholog of yeast Slx4, BTBD12, is an ATM substrate that functions as a scaffold for various DNA repair activities. Mutations human BTBD12 have been reported in new sub-type Fanconi anemia patients. Recent studies implicated the fly and worm orthologs, MUS312 HIM-18, regulation meiotic crossovers arising from double-strand break (DSB) initiating events also genome stability prior to meiosis. Using Btbd12 mutant mouse, we analyzed role gametogenesis. localizes pre-meiotic...