A5013822672- DNA Repair Mechanisms
- Genomics and Chromatin Dynamics
- Genetics and Neurodevelopmental Disorders
- Epigenetics and DNA Methylation
- RNA modifications and cancer
- RNA and protein synthesis mechanisms
- Gene Regulatory Network Analysis
- Single-cell and spatial transcriptomics
- PARP inhibition in cancer therapy
- Cancer Genomics and Diagnostics
- CRISPR and Genetic Engineering
- Protist diversity and phylogeny
- Genomics and Phylogenetic Studies
- Calcium signaling and nucleotide metabolism
- Chromosomal and Genetic Variations
- Fungal and yeast genetics research
Institut Curie
2019-2024
Université Paris Sciences et Lettres
2020-2023
Centre National de la Recherche Scientifique
2019-2023
Dynamique de l'information génétique : bases fondamentales et cancer
2021-2023
Sorbonne Université
2020-2023
University of Edinburgh
2019-2023
Université Paris 1 Panthéon-Sorbonne
2023
European Molecular Biology Laboratory
2015-2019
Babraham Institute
2014
DNA replication is temporally and spatially organized in all eukaryotes, yet the molecular control biological function of replication-timing program are unclear. Rif1 required for normal genome-wide regulation timing, but its poorly understood. Here we show that mouse embryonic stem cells, coats late-replicating domains and, with Lamin B1, identifies most genome. an essential determinant timing non-Lamin B1-bound late domains. We further demonstrate defines restricts interactions between...
Embryonic stem (ES) cells are in a dynamic equilibrium of distinct functional states, characterized by the heterogeneous expression critical pluripotency factors and regulated spectrum reversible histone modifications. Maintenance this is hallmark pluripotency. Here we find that ADP-ribosyltransferases Parp1 Parp7 play role safeguarding state occupying key genes, notably Nanog, Pou5f1, Sox2, Stella, Tet1 Zfp42, thereby protecting them from progressive epigenetic repression. In absence either...
Abstract Three-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing programme and, if so, how. Here we demonstrate that RIF1 is a molecular hub co-regulates both processes. Both depend upon interaction between PP1. However, whereas requires full complement of its with PP1, not sensitive dosage. The also extends beyond Availing this...
Crossovers generated during the repair of programmed meiotic double-strand breaks must be tightly regulated to promote accurate homolog segregation without deleterious outcomes, such as aneuploidy. The Mlh1-Mlh3 (MutLγ) endonuclease complex is critical for crossover resolution, which involves mechanistically unclear interplay between MutLγ and Exo1 polo kinase Cdc5. Using budding yeast gain temporal genetic traction on regulation, we find that constitutively interacts with Exo1. Upon...
Abstract Mammalian genomes are replicated in a cell type-specific order and coordination with transcription chromatin organization. Currently, single-cell replication studies require individual processing of sorted cells, yielding limited number (<100) cells. Here, we develop Kronos scRT, software for Replication Timing (scRT) analysis. scRT does not specific platform or sorting, which allows investigating large datasets obtained from asynchronous By applying our tool to published data as...
The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of genome. best-known mechanism controlling RT suppression late origins in heterochromatin by RIF1. Here, we report that antigen-activated, hypermutating murine B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin promotes early replication, but plays a minor role regulating origin activity, gene expression genome organization cells. Furthermore, find functions...
Abstract DNA replication is a vital process in all living organisms. At each cell division, > 30,000 origins are activated coordinated manner to ensure the duplication of 6 billion base pairs human genome. During differentiation and development, this program must adapt changes chromatin organization gene transcription: its deregulation can challenge genome stability, which leading cause many diseases including cancers neurological disorders. Over past decade, great progress has been made...
Summary Replication stress, a major hallmark of cancers, and ensuing genome instability source from impaired progression replication forks. The first line defense against fork slowing is compensation, long-described process that elicits firing otherwise dormant origins. It remains unclear whether compensation requires activation the DNA checkpoint or passively results lengthening window time during which origins can fire when slows, both. Using molecular combing we show here linear...
Eukaryotic genes are interrupted by introns that must be accurately spliced from mRNA precursors. With an average length of 25 nt, the more than 90,000 Paramecium tetraurelia stand among shortest reported in eukaryotes. The mechanisms specifying correct recognition these tiny remain poorly understood. Splicing can occur cotranscriptionally, and it has been proposed chromatin structure might influence splice site recognition. To investigate roles nucleosome positioning intron recognition, we...
ABSTRACT The mammalian DNA replication timing (RT) program is crucial for the proper functioning and integrity of genome. best-known mechanism controlling RT suppression late origins in heterochromatin by RIF1. Here, we report that antigen-activated B lymphocytes, RIF1 binds predominantly to early-replicating active chromatin, regulates early origin firing promotes replication. has a minor role gene expression genome organization cells. Furthermore, find functions complementary non-epistatic...
Abstract Three-dimensional genome organisation and replication timing are known to be correlated, however, it remains unknown whether nuclear architecture overall plays an instructive role in the replication-timing program and, if so, how. Here we demonstrate that RIF1 is a molecular hub co-regulates both processes. Both depend upon interaction between PP1. However, whereas requires full complement of its with PP1, not sensitive dosage. RIF1’s also extends beyond Availing this...
Summary Genome integrity requires replication to be completed before chromosome segregation. This coordination essentially relies on replication-dependent activation of a dedicated checkpoint that inhibits CDK1, delaying mitotic onset. Under-replication Common Fragile Sites (CFSs) however escapes surveillance, which triggers breakage. Using human cells, we asked here whether such leakage results from insufficient CDK1 inhibition under modest stresses used destabilize CFSs. We found tight...
<title>Abstract</title> Replication stress, a major hallmark of cancers, sources from replication fork slowing or blocking. In response, activation extra-origins, otherwise dormant, supports the rate. Whether DNA checkpoint drives this compensation process remained unclear. Here, combing analyses show that linear relationship ties inter-origin distances to speeds and slope line, called stressline, accurately quantifies efficiency. Comparison slopes in human cells with different genotypes...
Abstract Mammalian genomes are replicated in a cell-type specific order and coordination with transcription chromatin organization. Although the field of replication is also entering single-cell era, current studies require cell sorting, individual processing have yielded limited number (<100) cells. Here, we developed Kronos scRT ( https://github.com/CL-CHEN-Lab/Kronos_scRT ), software for Replication Timing (scRT) analysis. does not platform nor allowing investigation large datasets...
ABSTRACT Eukaryotic genes are interrupted by introns that must be accurately spliced from mRNA precursors. With an average length of 25 nt, the >90,000 Paramecium tetraurelia stand among shortest reported in eukaryotes. The mechanisms specifying correct recognition these tiny remain poorly understood. Splicing can occur co-transcriptionally and it has been proposed chromatin structure might influence splice site recognition. To investigate roles nucleosome positioning intron recognition,...