A5059054374- DNA Repair Mechanisms
- Telomeres, Telomerase, and Senescence
- Genomics and Chromatin Dynamics
- Chromosomal and Genetic Variations
- CRISPR and Genetic Engineering
- Advanced biosensing and bioanalysis techniques
- Mitochondrial Function and Pathology
- Microtubule and mitosis dynamics
- DNA and Nucleic Acid Chemistry
- Genomics and Phylogenetic Studies
- RNA Interference and Gene Delivery
- Carcinogens and Genotoxicity Assessment
- Bacterial Genetics and Biotechnology
- PARP inhibition in cancer therapy
- Genetics and Neurodevelopmental Disorders
- Click Chemistry and Applications
- Cancer therapeutics and mechanisms
- RNA Research and Splicing
- Nuclear Structure and Function
- Plant Genetic and Mutation Studies
- Genomic variations and chromosomal abnormalities
IFOM
2009-2025
Centre de Recherche en Cancérologie de Marseille
2022
Rockefeller University
2011-2016
University of Milan
2005-2009
Chromosome instability (CIN) is the most common form of genome and a hallmark cancer. CIN invariably leads to aneuploidy, state karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found aneuploid cells experience DNA replication stress in their first S-phase precipitate continuous This generates repertoire genetically diverse with structural chromosomal abnormalities either continue proliferating or stop dividing. Cycling display lower complexity compared arrested...
Transcription hinders replication fork progression and stability, the Mec1/ATR checkpoint protects integrity. Examining checkpoint-dependent mechanisms controlling we find that reversal dormant origin firing due to defects are rescued in mutants lacking THO, TREX-2, or inner-basket nucleoporins. Gene gating tethers transcribed genes nuclear periphery is counteracted by kinases through phosphorylation of nucleoporins such as Mlp1. Checkpoint fail detach from pores, thus generating topological...
DNA topoisomerases solve topological problems during chromosome metabolism. We investigated where and when Top1 Top2 are recruited on replicating chromosomes how their inactivation affects fork integrity damage checkpoint activation. show that, in the context of chromatin, act within a 600-base-pair (bp) region spanning moving forks. exhibits additional S-phase clusters at specific intergenic loci, mostly containing promoters. TOP1 ablation does not affect progression stability cause...
Shelterin protects chromosome ends from the DNA damage response. Although mechanism of telomere protection has been studied extensively, fate double-strand breaks (DSBs) inside telomeres is not known. Here, we report that telomere-internal FokI-induced DSBs activate ATM kinase-dependent signaling in S-phase but are well tolerated and repaired efficiently. Homologous recombination contributes to repair, leading increased length heterogeneity typical alternative lengthening (ALT) pathway....
Abstract Extrachromosomal telomeric circles are commonly invoked as important players in telomere maintenance, but their origin has remained elusive. Using electron microscopy analysis on purified telomeres we show that, apart from known structures, repeats accumulate internal loops (i-loops) that occur the proximity of nicks and single-stranded DNA gaps. I-loops induced by damage at normal represent majority structures detected ALT (Alternative Lengthening Telomeres) tumor cells. Our data...
Elia Zanella and Ylli Doksani IFOM ETS, The AIRC Institute of Molecular Oncology, 20139 Milan, Italy Correspondence: ylli.doksani{at}ifom.eu
The telomerase reverse transcriptase elongates telomeres to prevent replicative senescence. This process requires exposure of the 3'-end, which is thought occur when two sister are generated at replication completion. Using two-dimensional agarose gel electrophoresis (2D-gels) and electron microscopy, we found that telomeric repeats hotspots for fork reversal. Fork reversal generates 3' ends before To verify whether these elongated by telomerase, probed de novo synthesis in situ...
Homologous recombination factors play a crucial role in protecting nascent DNA during replication, but the of chromatin this process is largely unknown. Here, we used bacterial Tus/Ter barrier known to induce site-specific replication fork stalling S. cerevisiae. We report that Set1C subunit Spp1 recruited behind stalled independently its interaction with Set1. recruitment depends on PHD domain H3K4me3 parental histones deposited fork. Its prevents accumulation ssDNA at by restricting access...
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 Chromosome instability (CIN) is the most common form of genome and a hallmark cancer. CIN invariably leads to aneuploidy, state karyotype imbalance. Here, we show that aneuploidy can also trigger CIN. We found aneuploid cells experience DNA replication stress in their first S-phase precipitate continuous This generates repertoire genetically diverse either continue proliferating or stop dividing. Cycling display lower complexity compared arrested ones increased expression repair...
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 Extrachromosomal telomeric circles are commonly invoked as important players in telomere maintenance, but their origin has remained elusive. Using electron microscopy analysis on purified telomeres we show that, apart from known structures, repeats accumulate internal loops (i-loops), that occur proximity of nicks and single-stranded DNA gaps. I-loops induced by damage at normal represent the majority structures detected ALT (Alternative Lengthening Telomeres) tumor cells. Our data...
Abstract Homologous recombination factors play a crucial role in protecting nascent DNA during replication but the of chromatin this process is largely unknown. Here, we used bacterial Tus/ Ter barrier known to induce site-specific fork stalling S. cerevisiae . We report that COMPASS subunit Spp1 recruited behind stalled independently its interaction with Set1. recruitment depends on PHD domain H3K4me3 parental histones deposited fork. Its prevents accumulation ssDNA at by restricting access...