A5040094639- Redox biology and oxidative stress
- DNA Repair Mechanisms
- CRISPR and Genetic Engineering
- Protein Structure and Dynamics
- PARP inhibition in cancer therapy
- Enzyme Structure and Function
- Sulfur Compounds in Biology
- Genomics and Chromatin Dynamics
- Electron Spin Resonance Studies
- Metal-Catalyzed Oxygenation Mechanisms
- DNA and Nucleic Acid Chemistry
- RNA Interference and Gene Delivery
- Enzyme function and inhibition
- Microbial Inactivation Methods
- Nanopore and Nanochannel Transport Studies
- Glutathione Transferases and Polymorphisms
- Environmental Chemistry and Analysis
- RNA and protein synthesis mechanisms
- Bacillus and Francisella bacterial research
- Endoplasmic Reticulum Stress and Disease
- Synthesis and Characterization of Heterocyclic Compounds
- Environmental Toxicology and Ecotoxicology
- Heme Oxygenase-1 and Carbon Monoxide
- Plant Genetic and Mutation Studies
- Mass Spectrometry Techniques and Applications
Aix-Marseille Université
2011-2021
Centre National de la Recherche Scientifique
2011-2021
Inserm
2014-2020
Centre de Recherche en Cancérologie de Marseille
2014-2020
Cancer Research Center
2019-2020
Institut Paoli-Calmettes
2014-2020
Institut de Neurobiologie de la Méditerranée
2014
Canadian Nautical Research Society
2010
RAD51 promotes homologous recombination repair (HR) of double-strand breaks and acts during DNA replication to facilitate fork reversal protect nascent strands from nuclease digestion. Several additional HR proteins regulate protection by promoting filament formation. Here, we show that RADX modulates stalled antagonizing RAD51. Consequently, silencing restores in cells deficient for BRCA1, BRCA2, FANCA, FANCD2, or BOD1L. Inactivating prevents both MRE11- DNA2-dependent degradation....
Abstract Homologous recombination (HR) factors were recently implicated in DNA replication fork remodeling and protection. While maintaining genome stability, HR-mediated promotes cancer chemoresistance, by as-yet elusive mechanisms. Five HR cofactors – the RAD51 paralogs RAD51B, RAD51C, RAD51D, XRCC2 XRCC3 emerged as crucial tumor suppressors. Albeit extensively characterized repair, their role has not been addressed systematically. Here, we identify all while screening for modulators of...
Significance The mechanism of RAD51-recombinase filament formation is visualized and quantified with single-molecule resolution using a combination dual optical tweezers, fluorescence microscopy, microfluidics. With this method, short-lived transient intermediates formed during nascent RAD51 assembly were observed directly. It that nuclei consisting variable number monomers bind from solution to DNA, an interaction time increases nucleus size. Nuclei remain bound DNA long enough can grow by...
Article5 March 2018Open Access Source DataTransparent process Two distinct conformational states define the interaction of human RAD51-ATP with single-stranded DNA Ineke Brouwer Department Physics and Astronomy LaserLaB, Vrije Universiteit Amsterdam, The Netherlands Search for more papers by this author Tommaso Moschetti Biochemistry, University Cambridge, UK Andrea Candelli Edwige B Garcin Cancer Research Center Marseille, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille...
Deficiency in several of the classical human RAD51 paralogs [RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3] is associated with cancer predisposition Fanconi anemia. To investigate their functions, isogenic disruption mutants for each were generated non-transformed MCF10A mammary epithelial cells transformed U2OS HEK293 cells. In cells, viable ablated clones readily isolated paralog; contrast, exception RAD51B, are cell-essential Underlining importance genomic stability, mutant cell lines display...
Sulfate reducers have developed a multifaceted adaptative strategy to survive against oxidative stresses. Along with this stress response, we recently characterized an elegant reversible disulfide bond-dependent protective mechanism in the pyruvate:ferredoxin oxidoreductase (PFOR) of various Desulfovibrio species. Here, searched for thiol redox systems involved mechanism. Using fluorescent labeling, show that glutathione is not major thiol/disulfide balance-controlling compound four...
RAD51 is the key component of homologous recombination pathway in eukaryotic cells and performs its task by forming filaments on DNA. In this study we investigate physical properties formed DNA using nanofluidic channels fluorescence microscopy. Contrary to bacterial ortholog RecA, forms inhomogeneous long vitro, consisting several protein patches. We demonstrate that a permanent "kink" filament where two patches meet if stretch naked between short. The kinks are readily seen present...
Cytoplasmic desulfothioredoxin (Dtrx) from the anaerobe Desulfovibrio vulgaris Hildenborough has been identified as a new member of thiol disulfide oxidoreductase family. The active site Dtrx contains particular consensus sequence, CPHC, never seen in cytoplasmic thioredoxins and generally found periplasmic oxidases. Unlike canonical (Trx), does not present any reductase activity, but it presents instead an unusual isomerase activity. We have used NMR spectroscopy to gain insights into...
ABSTRACT Deficiency in several of the classical human RAD51 paralogs [RAD51B, RAD51C, RAD51D, XRCC2 and XRCC3] is associated with cancer predisposition Fanconi anemia. To investigate their functions, isogenic disruption mutants for each were generated non-transformed MCF10A mammary epithelial cells transformed U2OS HEK293 cells. In cells, viable ablated clones readily isolated paralog; contrast, exception RAD51B, are cell-essential Underlining importance genomic stability, mutant cell lines...
Abstract The proficiency of ovarian cancer cells to repair DNA double-strand breaks (DSBs) by homologous recombination (HR) is a key determinant in predicting response targeted therapies such as PARP inhibitors (PARPi). RAD51 paralogs act downstream BRCA1/2 facilitate HR. Numerous epidemiological studies have linked mutations the with hereditary predisposition. Despite their substantial links predisposition and development, paralog function during HR has remained elusive, part due...