A5074543116- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- DNA and Nucleic Acid Chemistry
- RNA Research and Splicing
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- PARP inhibition in cancer therapy
- RNA Interference and Gene Delivery
- Carcinogens and Genotoxicity Assessment
- Histone Deacetylase Inhibitors Research
- Chromosomal and Genetic Variations
- Ubiquitin and proteasome pathways
- Cholesterol and Lipid Metabolism
- Microtubule and mitosis dynamics
- Liver Disease Diagnosis and Treatment
- Cancer Genomics and Diagnostics
- Mechanisms of cancer metastasis
- Drug Transport and Resistance Mechanisms
- Viral Infections and Immunology Research
- HIV Research and Treatment
- Monoclonal and Polyclonal Antibodies Research
- Nuclear Structure and Function
- Adrenal Hormones and Disorders
Université de Toulouse
2016-2025
Centre National de la Recherche Scientifique
2016-2025
Centre de Biologie du Développement
2017-2022
Laboratoire de Biologie Cellulaire et Moléculaire du Contrôle de la Prolifération
2013-2022
Université Toulouse III - Paul Sabatier
2012-2022
Laboratoire de Biologie Moléculaire des Eucaryotes
2003-2019
Howard Hughes Medical Institute
2013
Institut de Biologie Moléculaire et Cellulaire
2013
The University of Texas at Austin
2013
European Bioinformatics Institute
2006
Modulating chromatin through histone methylation orchestrates numerous cellular processes. SETD2-dependent trimethylation of H3K36 is associated with active transcription. Here, we define a role for in homologous recombination (HR) repair human cells. We find that depleting SETD2 generates mutation signature resembling RAD51 depletion at I-SceI-induced DNA double-strand break (DSB) sites, significantly increased deletions arising microhomology-mediated end-joining. establish presynaptic...
Ataxia with oculomotor apraxia 2 (AOA-2) and amyotrophic lateral sclerosis (ALS4) are neurological disorders caused by mutations in the gene encoding for senataxin (SETX), a putative RNA:DNA helicase involved transcription maintenance of genome integrity. Here, using ChIP followed high throughput sequencing (ChIP-seq), we report that is recruited at DNA double-strand breaks (DSBs) when they occur transcriptionally active loci. Genome-wide mapping unveiled hybrids accumulate on DSB-flanking...
Programmable nucleases have enabled rapid and accessible genome engineering in eukaryotic cells living organisms. However, their delivery into target can be technically challenging when working with primary or vivo. Here, we use engineered murine leukemia virus-like particles loaded Cas9-sgRNA ribonucleoproteins (Nanoblades) to induce efficient genome-editing cell lines including human induced pluripotent stem cells, hematopoietic mouse bone-marrow cells. Transgene-free Nanoblades are also...
Highlights•DSB-chromatin landscape and HR/NHEJ chromatin signatures uncovered by ChIP-seq•H2BK120 undergoes a switch from ubiquitination to acetylation at local scale•H1 is removed ubiquitin accumulates on entire γH2AX domains, mainly HR DSB•53BP1 spreads over megabase-sized mostly in G1 HR-prone DSBsSummaryDouble-strand breaks (DSBs) are extremely detrimental DNA lesions that can lead cancer-driving mutations translocations. Non-homologous end joining (NHEJ) homologous recombination (HR)...
5' strand resection at DNA double breaks (DSBs) is critical for homologous recombination (HR) and genomic stability. Here we develop a novel method to quantitatively measure single-stranded intermediates in human cells find that the endonuclease-generated break sites resected up 3.5 kb cell cycle-dependent manner. Depletion of CtIP, Mre11, Exo1 or SOSS1 blocks resection, while depletion 53BP1, Ku DNA-dependent protein kinase catalytic subunit leads increased as measured by this method. While...
How chromatin shapes pathways that promote genome–epigenome integrity in response to DNA damage is an issue of crucial importance. We report human bromodomain (BRD)-containing proteins, the primary “readers” acetylated chromatin, are vital for (DDR). discovered more than one-third all BRD proteins change localization damage. identified ZMYND8 (zinc finger and MYND [myeloid, Nervy, DEAF-1] domain containing 8) as a novel DDR factor recruits nucleosome remodeling histone deacetylation (NuRD)...
Abstract The DNA damage response is essential to safeguard genome integrity. Although the contribution of chromatin in repair has been investigated 1,2 , chromosome folding these processes remains unclear 3 . Here we report that, after production double-stranded breaks (DSBs) mammalian cells, ATM drives formation a new compartment (D compartment) through clustering damaged topologically associating domains, decorated with γH2AX and 53BP1. This forms by mechanism that consistent...
Human DNA polymerase η (Pol η) is best known for its role in responding to UV irradiation-induced genome damage. We have recently observed that Pol also required the stability of common fragile sites (CFSs), whose rearrangements are considered a driving force oncogenesis. Here, we explored molecular mechanisms underlying this newly identified role. demonstrated accumulated at CFSs upon partial replication stress and could efficiently replicate non-B sequences within CFSs. deficiency led...
Upon DNA damage, histone modifications are dynamically reshaped to accommodate damage signaling and repair within chromatin. In this study, we report the identification of demethylase KDM5A as a key regulator bromodomain protein ZMYND8 NuRD (nucleosome remodeling deacetylation) complex in response. We observe KDM5A-dependent H3K4me3 demethylation chromatin near double-strand break (DSB) sites. Mechanistically, is required for ZMYND8–NuRD binding recruitment damage. Functionally, deficiency...
Chromatin undergoes major remodeling around DNA double-strand breaks (DSB) to promote repair and damage response (DDR) activation. We recently reported a high-resolution map of γH2AX multiple on the human genome, using new cell-based DSB inducible system. In an attempt further characterize chromatin landscape induced DSBs, we now report profile SMC3, subunit cohesin complex, previously characterized as required for by homologous recombination. found that recruitment is moderate restricted...
DNA double-strand breaks (DSBs) elicit the so-called damage response (DDR), largely relying on ataxia telangiectasia mutated (ATM) and DNA-dependent protein kinase (DNA-PKcs), two members of PI3K-like family, whose respective functions during sequential steps DDR remains controversial. Using DIvA system (DSB inducible via AsiSI) combined with high-resolution mapping advanced microscopy, we uncovered that both ATM DNA-PKcs spread in cis a confined region surrounding DSBs, independently...
DNA double-strand breaks (DSBs) are highly toxic lesions that can be rapidly repaired by 2 main pathways, namely Homologous Recombination (HR) and Non End Joining (NHEJ). The choice between these pathways is a critical, yet not completely understood, aspect of DSB repair. We recently found distinct DSBs induced across the genome same pathway. Indeed, in active genes, naturally enriched trimethyl form histone H3 lysine 36 (H3K36me3), channeled to repair HR, manner depending on SETD2, major...
The ribosomal DNA (rDNA) represents a particularly unstable locus undergoing frequent breakage. double-strand breaks (DSBs) within rDNA induce both transcriptional repression and nucleolar segregation, but the link between two events remains unclear. Here we found that DSBs induced on trigger in cohesin- HUSH (human silencing hub) complex-dependent manner throughout cell cycle. In S/G2 cells, is further followed by extended resection interior of nucleolus, DSB mobilization at periphery caps,...