A5063444330- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- RNA Research and Splicing
- CRISPR and Genetic Engineering
- Fungal and yeast genetics research
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Corrosion Behavior and Inhibition
- Concrete Corrosion and Durability
- Anodic Oxide Films and Nanostructures
- Genetic Mapping and Diversity in Plants and Animals
- Carcinogens and Genotoxicity Assessment
- DNA and Nucleic Acid Chemistry
- Chromosomal and Genetic Variations
- Nuclear Structure and Function
- Molecular Biology Techniques and Applications
- Epigenetics and DNA Methylation
- Plant Genetic and Mutation Studies
- Metabolism and Genetic Disorders
- Plant-Microbe Interactions and Immunity
- Chromatin Remodeling and Cancer
- Hydrogen embrittlement and corrosion behaviors in metals
- Wheat and Barley Genetics and Pathology
- Bacteriophages and microbial interactions
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2016-2025
Universidad de Sevilla
2016-2025
Universidad Pablo de Olavide
2017-2024
Consejo Superior de Investigaciones Científicas
2007-2021
University of California, Davis
2020
Airbus (Spain)
2009-2016
Unidades Centrales Científico-Técnicas
2011
Universidad Autónoma de Madrid
2009-2010
Co-transcriptional RNA-DNA hybrids (R loops) cause genome instability. To prevent harmful R loop accumulation, cells have evolved specific eukaryotic factors, one being the BRCA2 double-strand break repair protein. As also protects stalled replication forks and is FANCD1 member of Fanconi Anemia (FA) pathway, we investigated FA role in loop-dependent Using human murine defective FANCD2 or FANCA primary bone marrow from deficient mice, show that pathway removes loops, many DNA breaks...
FACT (facilitates chromatin transcription) is a chromatin-reorganizing complex that swaps nucleosomes around the RNA polymerase during transcription elongation and has role in replication not fully understood yet. Here we show recombination factors are required for survival of yeast mutants, consistent with an accumulation DNA breaks detected by Rad52 foci transcription-dependent hyperrecombination. Breaks also accumulate FACT-depleted human cells, as shown γH2AX single-cell electrophoresis....
Increasing evidences suggest that nuclear pore complexes (NPCs) control different aspects of metabolism, including transcription, organization, and DNA repair. We previously established the Nup84 complex, a major NPC building block, is part genetic network involved in Here, we show double-strand break (DSB) appearance linked to shared function Nup60/Mlp1-2 complexes. Mutants within these exhibit similar interactions alteration repair processes as mutants SUMO-protease Ulp1. Consistently,...
Transcription is a major obstacle for replication fork (RF) progression and cause of genome instability. Part this instability mediated by cotranscriptional R loops, which are believed to increase suboptimal assembly the nascent messenger ribonucleoprotein particle (mRNP). However, no clear evidence exists that heterogeneous nuclear RNPs (hnRNPs), basic mRNP components, prevent R-loop stabilization. Here we show yeast Npl3, most abundant RNA-binding hnRNP, prevents R-loop-mediated npl3Δ...
R loops are an important source of genome instability, largely due to their negative impact on replication progression. Yra1/ALY is abundant RNA-binding factor conserved from yeast humans and required for mRNA export, but its excess causes lethality instability. Here, we show that, in addition ssDNA ssRNA, Yra1 binds RNA–DNA hybrids vitro and, when artificially overexpressed, can be recruited chromatin hybrid-dependent manner, stabilizing converting them into obstacles vivo. Importantly,...
Abstract Identifying how R-loops are generated is crucial to know transcription compromises genome integrity. We show by genome-wide analysis of conditional yeast mutants that the THO complex, prevents R-loop formation in G1 and S-phase, whereas Sen1 DNA-RNA helicase them only S-phase. Interestingly, damage accumulates asymmetrically downstream replication fork sen1 cells but symmetrically hpr1 mutant. Our results indicate that: form co-transcriptionally independently DNA replication; a...
Unscheduled R loops can be a source of genome instability, hallmark cancer cells. Although targeted proteomic approaches and cellular analysis specific mutants have uncovered factors potentially involved in R-loop homeostasis, we report more open screening whose depletion causes based on the ability activation-induced cytidine deaminase (AID) to target loops. Immunofluorescence γH2AX caused by small interfering RNAs (siRNAs) covering 3,205 protein-coding genes identifies 59 potential...
AbstractHpr1 forms, together with Tho2, Mft1, and Thp2, the THO complex, which controls transcription elongation genome stability in Saccharomyces cerevisiae. Mutations genes encoding complex confer strong transcription-impairment hyperrecombination phenotypes bacterial lacZgene. In this work we demonstrate that Hpr1 is a factor required for of long as well G+C-rich DNA sequences. Using different lacZ segments fused to GAL1promoter, show negative effect lacZsequences on depends their...
THO/TREX is a conserved eukaryotic complex formed by the core THO plus proteins involved in mRNA metabolism and export such as Sub2 Yra1. Mutations any of structural genes cause pleiotropic phenotypes transcription impairment, increased transcription-associated recombination, defects. To assay relevance transcription, we performed vitro elongation assays mutant cell extracts using supercoiled DNA templates containing two G-less cassettes. With these assays, demonstrate that hpr1delta,...
RNA polymerases frequently deal with a number of obstacles during transcription elongation that need to be removed for resumption. One important type hindrance consists DNA lesions, which are by transcription-coupled repair (TC-NER), specific sub-pathway nucleotide excision repair. To improve our knowledge and its coupling TC-NER, we used the yeast library non-essential knock-out mutations screen genes conferring resistance transcription-elongation inhibitor mycophenolic acid DNA-damaging...
Abstract Perturbation in the replication-stress response (RSR) and DNA-damage (DDR) causes genomic instability. Genomic instability occurs Wiskott-Aldrich syndrome (WAS), a primary immunodeficiency disorder, yet mechanism remains largely uncharacterized. Replication protein A (RPA), single-strand DNA (ssDNA) binding protein, has key roles RSR DDR. Here we show that human WAS-protein (WASp) modulates RPA functions at perturbed replication forks (RFs). Following genotoxic insult, WASp...