A5047936626- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Genomics and Chromatin Dynamics
- Fungal and yeast genetics research
- RNA Research and Splicing
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- Plant Genetic and Mutation Studies
- Microtubule and mitosis dynamics
- Mitochondrial Function and Pathology
- DNA and Nucleic Acid Chemistry
- RNA regulation and disease
- Carcinogens and Genotoxicity Assessment
- Genetic Mapping and Diversity in Plants and Animals
- RNA and protein synthesis mechanisms
- Photosynthetic Processes and Mechanisms
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- Rice Cultivation and Yield Improvement
- Genetic Neurodegenerative Diseases
- Plant Pathogens and Fungal Diseases
- Bacterial Genetics and Biotechnology
- Molecular Biology Techniques and Applications
- Genetically Modified Organisms Research
- Chromosomal and Genetic Variations
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2008-2024
Universidad de Sevilla
2008-2024
Consejo Superior de Investigaciones Científicas
2007-2024
Universidad Pablo de Olavide
2017-2022
University of California, Davis
2020-2021
The Francis Crick Institute
2018
Cancer Research UK
2013
Sen1 of S. cerevisiae is a known component the NRD complex implicated in transcription termination nonpolyadenylated as well some polyadenylated RNA polymerase II transcripts. We now show that helicase possesses wider function by restricting occurrence RNA:DNA hybrids may naturally form during transcription, when nascent hybridizes to DNA prior its packaging into protein complexes. These displace nontranscribed strand and create R loop structures. Loss results transient accumulation so...
THO/TREX connects transcription with genome integrity in yeast, but a role of mammalian THO these processes is uncertain, which suggests differential implication mRNP biogenesis factors yeast and humans. We show that human depletion impairs elongation mRNA export increases instability associated DNA breaks, leading to hyper-recombination γH2AX 53BP1 foci accumulation. This accompanied by replication alteration as determined combing. Genome R-loop-dependent, deduced from the ability AID...
Transcription hinders replication fork progression and stability, the Mec1/ATR checkpoint protects integrity. Examining checkpoint-dependent mechanisms controlling we find that reversal dormant origin firing due to defects are rescued in mutants lacking THO, TREX-2, or inner-basket nucleoporins. Gene gating tethers transcribed genes nuclear periphery is counteracted by kinases through phosphorylation of nucleoporins such as Mlp1. Checkpoint fail detach from pores, thus generating topological...
DNA topoisomerase I can contribute to cancer genome instability. During catalytic activity, forms a transient intermediate, I–DNA cleavage complex (Top1cc) allow strand rotation and duplex relaxation, which lead elevated levels of DNA-RNA hybrids micronuclei. To comprehend the underlying mechanisms, we have integrated genomic data Top1cc-triggered double-strand breaks (DSBs) shortly after Top1cc induction, revealing that Top1ccs increase hybrid with different mechanisms. DSBs are at highly...
The eukaryotic THO/TREX complex, involved in mRNP biogenesis, plays a key role the maintenance of genome integrity yeast. mRNA export factors such as Thp1-Sac3 also affect integrity, but their mutations have other phenotypes different from those THO/TREX. Sus1 is novel component SAGA transcription factor that associates with Thp1-Sac3, little known about its effect on instability and transcription. Here we show Thp1, Sac3, form functional unit biogenesis independent SAGA. Importantly,...
Activation-induced cytidine deaminase (AID) is a B cell enzyme essential for Ig somatic hypermutation and class switch recombination. AID acts on ssDNA, regions of genes, target AID, form R-loops that contain ssDNA. Nevertheless, how action specifically targeted to particular DNA sequences not clear. Because mutations altering cotranscriptional messenger ribonucleoprotein (mRNP) formation such as those in THO/TREX yeast promote R-loops, we investigated whether the assembly mRNPs could affect...
AbstractCotranscriptional R-loops are formed in yeast mutants of the THO complex, which functions at interface between transcription and mRNA export. Despite relevance transcription-associated recombination, mechanisms by they trigger recombination still elusive. In order to understand how compromise genome stability, we have analyzed genetic interaction with 26 genes involved replication, S-phase checkpoint, DNA repair, chromatin remodeling. We found a synthetic growth defect double null...
RNA-DNA hybrids are naturally occurring obstacles that must be overcome by the DNA replication machinery. In absence of RNase H enzymes, accumulate, resulting in stress, damage and compromised genomic integrity. We demonstrate Mph1, yeast homolog Fanconi anemia protein M (FANCM), is required for cell viability enzymes. The integrity Mph1 helicase domain crucial to prevent accumulation hybrid-dependent damage, as determined Rad52 foci. forms foci when e.g. or THO-complex mutants at short...
DNA double-strand breaks (DSBs) are the most harmful lesions and their repair is crucial for cell viability genome integrity. The readout of DSB may depend on whether DSBs occur at transcribed versus non-transcribed regions. Some studies have postulated that DNA-RNA hybrids form to promote recombinational repair, but others challenged this notion. To directly assess formed or interfere with we used plasmid chromosomal-based systems analysis DSB-induced recombination in
Transcription of the switch (S) regions immunoglobulin genes in B cells generates stable R-loops that are targeted by Activation Induced Cytidine Deaminase (AID), triggering class recombination (CSR), as well translocations with c-MYC responsible for Burkitt's lymphomas. In Saccharomyces cerevisiae, formed co-transcriptionally mutants THO, a conserved nuclear complex involved mRNP biogenesis. Such trigger genome instability and facilitate deamination human AID. To understand mechanisms...
AbstractDouble-strand breaks (DSBs) are harmful DNA lesions that can generate chromosomal rearrangements or chromosome losses if not properly repaired. Despite their association with a number of genetic diseases and cancer, the mechanisms by which DSBs cause remain unknown. Using newly developed experimental assay for analysis translocations occurring between two chromosomes in Saccharomyces cerevisiae, we found single DSB located on one uses short homologous sequence third as bridge to...