A5005759525- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- Microtubule and mitosis dynamics
- Epigenetics and DNA Methylation
- Genetics and Neurodevelopmental Disorders
- BRCA gene mutations in cancer
- Genomic variations and chromosomal abnormalities
- Advanced biosensing and bioanalysis techniques
- Genomics and Phylogenetic Studies
- Mitochondrial Function and Pathology
- Cancer therapeutics and mechanisms
- CRISPR and Genetic Engineering
- Plant Genetic and Mutation Studies
- PARP inhibition in cancer therapy
- Cancer-related Molecular Pathways
- Carcinogens and Genotoxicity Assessment
Université Paris Sciences et Lettres
2016-2024
Centre National de la Recherche Scientifique
2010-2024
Sorbonne Université
2013-2024
Institut Gustave Roussy
2016-2024
Université Paris-Saclay
2016-2024
Institut Curie
2013-2024
University of Geneva
2019
Université Paris Cité
2016
Université Paris-Sud
2013
Dynamique de l'information génétique : bases fondamentales et cancer
2010
Abstract Replication stress, a hallmark of cancerous and pre-cancerous lesions, is linked to structural chromosomal aberrations. Recent studies demonstrated that it could also lead numerical instability (CIN). The mechanism, however, remains elusive. Here, we show inducing replication stress in non-cancerous cells stabilizes spindle microtubules favours premature centriole disengagement, causing transient multipolar spindles lagging chromosomes micronuclei. Premature disengagement depends on...
Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of centromere-specific histone H3 variant CENP-A in safeguarding replication alpha-satellite repeats structural aneuploidy. Rapid removal S phase, but not other cell-cycle stages, caused accumulation R...
Abstract Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These promote oncogenesis by dysregulating gene expression through alterations of modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability H3.3 mutant pHGG, opens new therapeutic options. The two most frequent K27M G34R, drive replication-associated damage non-homologous end joining (NHEJ). Aberrant NHEJ is...
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...
Replications forks are routinely hindered by different endogenous stresses. Because homologous recombination plays a pivotal role in the reactivation of arrested replication forks, defects reveal initial stress(es). Homologous recombination-defective cells consistently exhibit spontaneously reduced speed, leading to mitotic extra centrosomes. Here, we identify oxidative stress as major source speed deceleration cells. The treatment with antioxidant N-acetyl-cysteine or maintenance at low O2...
Centromeres are key elements for chromosome segregation. Canonical centromeres built over long-stretches of tandem repetitive arrays. Despite being quite abundant compared to other loci, centromere sequences overall still represent only 2 5% the human genome, therefore studying their genetic and epigenetic features is a major challenge. Furthermore, sequencing centromeric regions requires high coverage fully analyze length sequence variations, this can be extremely costly. To bypass these...
Abstract Centromeres are key elements for chromosome segregation. Canonical centromeres built over long-stretches of tandem repetitive arrays. Despite being quite abundant compared to other loci, centromere sequences overall still represent only 2 5% the human genome, therefore studying their genetic and epigenetic features is a major challenge. Furthermore, sequencing centromeric regions requires high coverage fully analyze length sequence variations, which can be extremely costly. To...
Abstract Chromosome segregation relies on centromeres, yet their repetitive DNA is often prone to aberrant rearrangements under pathological conditions. Factors that maintain centromere integrity prevent centromere-associated chromosome translocations are unknown. Here, we demonstrate the importance of centromere-specific histone H3 variant CENP-A in safeguarding replication alpha-satellite repeats structural aneuploidy. Rapid removal S-phase, but not other cell cycle stages, caused...
Received: September 24, 2010 , Accepted: December 16, Published: // Endogenous replicative stress could be one trigger leading to tumor initiation: indeed, activation of the DNA damage response (DDR), considered result stress, is observed in pre-cancerous cells; moreover, hereditary breast cancers, almost all genes affected relate DDR. The most frequently mutated gene BRCA1, essential for homologous recombination (HR), a fundamental process maintaining genome stability that permits...
Summary Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These promote oncogenesis by dysregulating gene expression through alterations of modifications. We identify aberrant DNA repair as an independent oncogenic mechanism, which fosters genome instability tumor cell growth H3.3 mutant pHGG, thus opening new therapeutic options. The two most frequent K27M G34R, drive replication-associated damage non-homologous end...
The high incidence of whole-arm chromosome aneuploidy and translocations in tumors suggests an intrinsic instability centromeres, unique chromosomal loci built on large stretches repetitive sequences. causes behind this fragility the mechanisms acting to preserve centromere integrity remain elusive. Here, we show that replication stress, a hallmark (pre-)cancerous lesions, promotes non-random breakage mitosis, also observed panel ex-vivo patient-derived ovarian cancer models along with...