A5078086437- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- CRISPR and Genetic Engineering
- Epigenetics and DNA Methylation
- Genomic variations and chromosomal abnormalities
- Biochemical and Molecular Research
- RNA and protein synthesis mechanisms
- Peptidase Inhibition and Analysis
- RNA modifications and cancer
- Microtubule and mitosis dynamics
- Molecular Biology Techniques and Applications
- Signaling Pathways in Disease
- Chromosomal and Genetic Variations
- RNA Research and Splicing
- DNA and Nucleic Acid Chemistry
- Cancer-related Molecular Pathways
- Mitochondrial Function and Pathology
- Genomics and Rare Diseases
- PARP inhibition in cancer therapy
- Fungal and yeast genetics research
- Ubiquitin and proteasome pathways
- RNA Interference and Gene Delivery
- Telomeres, Telomerase, and Senescence
- HIV/AIDS drug development and treatment
Sorbonne Université
2015-2024
Institut Gustave Roussy
2016-2024
Centre National de la Recherche Scientifique
2012-2023
Université Paris 1 Panthéon-Sorbonne
2023
Institut Curie
2007-2019
Université Paris Sciences et Lettres
2016-2019
Sorbonne University Abu Dhabi
2019
La Ligue Contre le Cancer
2018
Université Paris Cité
2014-2016
Laboratoire d'études sur les monothéismes
2016
Correct replication of the genome and protection its integrity are essential for cell survival. In a high-throughput screen studying H2AX phosphorylation, we identified Wee1 as regulator genomic stability. down-regulation not only induced phosphorylation but also triggered general deoxyribonucleic acid (DNA) damage response (DDR) caused block in DNA replication, resulting accumulation cells S phase. Wee1-deficient showed decrease fork speed, demonstrating involvement replication. Inhibiting...
Cancer genomes exhibit numerous deletions, some of which inactivate tumor suppressor genes and/or correspond to unstable genomic regions, notably common fragile sites (CFSs). However, 70%–80% recurrent deletions cataloged in tumors remain unexplained. Recent findings that CFS setting is cell-type dependent prompted us reevaluate the contribution cancer deletions. By combining extensive molecular mapping and a comprehensive analysis features, we show pool CFSs for all human cell types...
Breaks at common fragile sites (CFS) are a recognized source of genome instability in pre-neoplastic lesions, but how such checkpoint-proficient cells escape surveillance and continue cycling is unknown. Here we show, lymphocytes fibroblasts, that moderate replication stresses like those inducing breaks CFSs trigger chromatin loading sensors mediators the ATR pathway fail to activate Chk1 or p53. Consistently, found depleted ATR, not Chk1, accumulate single-stranded DNA upon Mre11-dependent...
Abstract Common fragile sites (CFSs) are chromosome regions prone to breakage upon replication stress known drive rearrangements during oncogenesis. Most CFSs nest in large expressed genes, suggesting that transcription could elicit their instability; however, the underlying mechanisms remain elusive. Genome-wide timing analyses here show stress-induced delayed/under-replication is hallmark of CFSs. Extensive genome-wide nascent transcripts, origin positioning and fork directionality reveal...
Amplification of the epidermal growth factor receptor gene on double minutes is recurrently observed in cells advanced gliomas, but structure these extrachromosomal circular DNA molecules and mechanisms responsible for their formation are still poorly understood. By using quantitative PCR chromosome walking, we investigated genetic content organization repeats seven gliomas. It was established that all amplicons a given tumor derive from single founding molecule. In each molecule generated...
Highlights•Nuclease-dependent DNA damage events are induced in Chk1-deficient cells•Activation of the ATM pathway limits precursors available for replication•DNA precursor starvation elicits replication fork slowing these cells•Origin firing is fine-tuned by speed independently Chk1 statusSummaryMammalian cells deficient ATR or display moderate and increased initiation density, but underlying mechanisms have remained unclear. We show that exogenous deoxyribonucleosides suppress both...
Significance Faithful genome duplication requires the precise coordination of DNA replication, repair/recombination and chromosome segregation. Homologous recombination (HR) plays a pivotal role in resumption blocked replication forks, HR − cells exhibit both spontaneous slower genome-wide fork speed mitotic extra centrosomes (MECs). We show that MECs result from slow kinetics are associated with multipolar mitosis leading to general unbalanced Thus, low levels stress, which not detected by...
Faithful DNA replication is essential for the maintenance of genome integrity.Incomplete leads to breaks and chromosomal rearrangements, which are causal factors in cancer other human diseases.Despite their importance, molecular mechanisms that control stability incompletely understood.Here, we report a pathway required stability.This has three components: an E3 ubiquitin ligase, transcriptional repressor, protein.The ligase RBBP6 ubiquitinates destabilizes repressor ZBTB38.This negatively...
Various studies suggest a tight relationship between chromosome rearrangements driving tumor progression and breaks at loci called common fragile sites. Most of these sites are induced after perturbation the replication dynamics, notably by aphidicolin treatment. We have mapped majority to interface R G bands, which calls into question previous assignment aphidicolin-sensitive bands. This observation suggests that most them correspond ensure transition early late replicating domains. show...