A5040924595- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- RNA Research and Splicing
- Microtubule and mitosis dynamics
- PARP inhibition in cancer therapy
- DNA and Nucleic Acid Chemistry
- Genomics and Chromatin Dynamics
- Mycobacterium research and diagnosis
- RNA Interference and Gene Delivery
- Advanced biosensing and bioanalysis techniques
- RNA modifications and cancer
- Cancer-related Molecular Pathways
- Tuberculosis Research and Epidemiology
- Ubiquitin and proteasome pathways
- Mitochondrial Function and Pathology
- Photosynthetic Processes and Mechanisms
- Endoplasmic Reticulum Stress and Disease
- Advanced Breast Cancer Therapies
- Carcinogens and Genotoxicity Assessment
- RNA and protein synthesis mechanisms
- Chromosomal and Genetic Variations
- Cancer-related gene regulation
- Infectious Diseases and Tuberculosis
- Fungal and yeast genetics research
- Peptidase Inhibition and Analysis
Centro Andaluz de Biología Molecular y Medicina Regenerativa
2016-2025
Universidad de Sevilla
2016-2025
Universidad Pablo de Olavide
2017-2025
Consejo Superior de Investigaciones Científicas
2015-2025
Junta de Andalucía
2023-2024
IVI Sevilla Clinic
2021
National Agricultural Technology Institute
2018-2021
Consejo Nacional de Investigaciones Científicas y Técnicas
2020-2021
Centro Científico Tecnológico - San Juan
2018
Consejo Nacional de Ciencia y Tecnología
2014
In G(0) and G(1), DNA double strand breaks are repaired by nonhomologous end joining, whereas in S G(2), they also homologous recombination. The human CtIP protein controls break (DSB) resection, an event that occurs effectively only S/G(2) promotes recombination but not non-homologous joining. Here, we mutate a highly conserved cyclin-dependent kinase (CDK) target motif reveal mutating Thr-847 to Ala impairs it Glu mimic constitutive phosphorylation does not. Moreover, show unlike cells...
DNA-end resection is a highly regulated and critical step in the response repair of DNA double-strand breaks. In higher eukaryotes, CtIP regulates by integrating cellular signals via its posttranslational modifications protein-protein interactions, including cell-cycle-controlled interaction with BRCA1. The role BRCA1 not clear. Here, we develop an assay to study eukaryotes at high resolution. We demonstrate that BRCA1-CtIP interaction, albeit essential for resection, modulates speed which...
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,...
Seckel syndrome is a recessively inherited dwarfism disorder characterized by microcephaly and unique head profile. Genetically, it constitutes heterogeneous condition, with several loci mapped (SCKL1-5) but only three disease genes identified: the ATR, CENPJ, CEP152 that control cellular responses to DNA damage. We previously locus chromosome 18p11.31-q11.2 (SCKL2). Here, we report two mutations in CtIP (RBBP8) gene within this result expression of C-terminally truncated forms CtIP. propose...
Abstract The exosome is a ribonucleolytic complex that plays important roles in RNA metabolism. Here we show the necessary for repair of DNA double-strand breaks (DSBs) human cells and clearance an essential step homologous recombination. Transcription DSB-flanking sequences results production damage-induced long non-coding RNAs (dilncRNAs) engage DNA-RNA hybrid formation. Depletion EXOSC10, catalytic subunit, leads to increased dilncRNA levels. Moreover, targeting ssDNA-binding protein RPA...
Abstract The maintenance of genomic stability requires the coordination multiple cellular tasks upon appearance DNA lesions. RNA editing, post-transcriptional sequence alteration RNA, has a profound effect on cell homeostasis, but its implication in response to damage was not previously explored. Here we show that, breaks, an overall change Adenosine-to-Inosine editing is observed, phenomenon call R NA E diting DA mage esponse (REDAR). REDAR relies checkpoint kinase ATR and recombination...
DNA replication faces challenges from lesions originated endogenous or exogenous sources of stress, leading to the accumulation single-stranded (ssDNA) that triggers activation ATR checkpoint response. To complete genome in presence damaged DNA, cells employ damage tolerance mechanisms operate not only at stalled forks but also ssDNA gaps by repriming synthesis downstream lesions. Here, we demonstrate human accumulate post-replicative following replicative stress induction. These gaps,...
DNA double strand breaks are the most cytotoxic lesions that can occur on DNA. They be repaired by different mechanisms and optimal survival requires a tight control between them. Here we uncover protein deneddylation as major controller of repair pathway choice. Neddylation inhibition changes normal profile toward an increase homologous recombination. Indeed, RNF111/UBE2M-mediated neddylation acts inhibitor BRCA1 CtIP-mediated end resection, key process in By controlling length ssDNA...
There are two major and alternative pathways to repair DNA double-strand breaks: non-homologous end-joining homologous recombination. Here we identify characterize novel factors involved in choosing between these pathways; this study took advantage of the SeeSaw Reporter, which breaks by homology-independent or -dependent mechanisms is distinguished accumulation green red fluorescence, respectively. Using a genome-wide human esiRNA (endoribonuclease-prepared siRNA) library, isolate genes...
Highlights•PIF1 is involved in DNA resection•G-quadruplexes impair resection•PIF1 required to resect over sequences prone forming G-quadruplexes•PIF1 interacts with BRCA1 resolve G-quadruplexes at breaksSummaryDNA breaks are complex lesions that can be repaired either by non-homologous end joining (NHEJ) or homologous recombination (HR). The decision between these two routes of repair a key point the damage response (DDR) controlled resection. core machinery catalyzing resection process well...
DNA double-strand break (DSB) repair is initiated by end resection. CtIP acts in short-range resection to stimulate MRE11–RAD50–NBS1 (MRN) endonucleolytically cleave 5′-terminated bypass protein blocks. also promotes the DNA2 helicase–nuclease accelerate long-range downstream from MRN. Here, using AlphaFold2, we identified CtIP-F728E-Y736E as a separation-of-function mutant that still proficient conjunction with MRN but not able ssDNA degradation DNA2. Accordingly, impairs physical...
Abstract Deficiencies in the BRCA1 tumor suppressor gene are main cause of hereditary breast and ovarian cancer. is involved Homologous Recombination DNA repair pathway and, together with BARD1, forms a heterodimer ubiquitin E3 activity. The relevance BRCA1/BARD1 activity for suppression remains controversial. Here, we observe that not required or resistance to Olaparib. Using TULIP2 methodology, which enables direct identification E3-specific ubiquitination substrates, identify substrates...
Abstract Background Tumor resistance represents a major challenge in the current oncology landscape. Asparagine endopeptidase (AEP) overexpression correlates with worse prognosis and reduced overall survival most human solid tumors. However, underlying mechanisms of connection between AEP cancer patients remain unclear. Methods High-throughput proteomics, cellular molecular biology approaches clinical data from breast (BC) were used to identify novel, biologically relevant targets....
Abstract Background Tumor resistance represents a major challenge in the current oncology landscape. Asparagine endopeptidase (AEP) overexpression correlates with worse prognosis and reduced overall survival most human solid tumors. However, underlying mechanisms of connection between AEP cancer patients remain unclear. Methods High-throughput proteomics, cellular molecular biology approaches clinical data from breast (BC) were used to identify novel, biologically relevant targets....
Abstract SRSF2 (serine/arginine-rich splicing factor 2) is a critical regulator of pre-messenger RNA splicing, which also plays noncanonical functions in transcription initiation and elongation. Although elevated levels are associated with advanced stages lung adenocarcinoma (LUAD), the mechanisms connecting to tumor progression remain unknown. We show that overexpression increases global replicative stress LUAD cells, correlates production DNA damage, notably double-strand breaks (DSBs),...