Chromosomal Domains and DNA Replication





During development, chromosomal domains of expression are structured as cells actively divide. Before each division, cells must copy their genome as accuratly as possible or risk cell death or genomic instability leading to the establishment of cancer cells. This process is called DNA replication and starts at multiple specific sites (~100,000 in humans), called origins of replication. A spatiotemporal program controls the positioning and the activation time of the origins of replication during the S phase of the cell cycle. The goal of the team is to identify the molecular mechanisms that implement this program. More recently, we are also trying to understand how two fundamental processes, transcription and replication, act on the same molecule simultaneously in the most harmonious way possible. Indeed, it is now clearly established that conflicts between these two machineries can be a source of genomic instability.


Group Leader: Marie-Noëlle PRIOLEAU

Research Director, Inserm

+33 (0)157278102








Research Topics


Biologie quantitative et modélisation , Développement et évolution , Dynamique cellulaire et signalisation , Dynamique du génome et des chromosomes, Pathologies moléculaires et cellulaires


Selected publications


1) Clustering of strong replicators associated with active promoters is sufficient to establish an early-replicating domain. Brossas C, Valton AL, Venev SV, Chilaka S, Counillon A, Laurent M, Goncalves C, Duriez B, Picard F, Dekker J, Prioleau MN. EMBO J. 2020 Nov 2;39(21):e99520. doi: 10.15252/embj.201899520. Epub 2020 Sep 16. PMID: 32935369


2) Replication dynamics of individual loci in single living cells reveal changes in the degree of replication stochasticity through S phase. Duriez B, Chilaka S, Bercher JF, Hercul E, Prioleau MN. Nucleic Acids Res. 2019 Jun 4;47(10):5155-5169. doi: 10.1093/nar/gkz220. PMID: 30926993


3) Evolution of replication origins in vertebrate genomes: rapid turnover despite selective constraints. Massip F, Laurent M, Brossas C, Fernández-Justel JM, Gómez M, Prioleau MN, Duret L, Picard F. Nucleic Acids Res. 2019 Jun 4;47(10):5114-5125. doi: 10.1093/nar/gkz182. PMID: 30916335


4) Transcription-dependent regulation of replication dynamics modulates genome stability. Blin M, Le Tallec B, Nähse V, Schmidt M, Brossas C, Millot GA, Prioleau MN, Debatisse M. Nat Struct Mol Biol. 2019 Jan;26(1):58-66. doi: 10.1038/s41594-018-0170-1. Epub 2018 Dec 31. PMID: 30598553


5) The spatiotemporal program of DNA replication is associated with specific combinations of chromatin marks in human cells. Picard F, Cadoret JC, Audit B, Arneodo A, Alberti A, Battail C, Duret L, Prioleau MN. PLoS Genet. 2014 May 1;10(5):e1004282. doi: 10.1371/journal.pgen.1004282. eCollection 2014 May. PMID: 24785686


6) G4 motifs affect origin positioning and efficiency in two vertebrate replicators. Valton AL, Hassan-Zadeh V, Lema I, Boggetto N, Alberti P, Saintomé C, Riou JF, Prioleau MN. EMBO J. 2014 Apr 1;33(7):732-46. doi: 10.1002/embj.201387506. Epub 2014 Feb 12. PMID: 24521668


7) USF binding sequences from the HS4 insulator element impose early replication timing on a vertebrate replicator. Hassan-Zadeh V, Chilaka S, Cadoret JC, Ma MK, Boggetto N, West AG, Prioleau MN. PLoS Biol. 2012;10(3):e1001277. doi: 10.1371/journal.pbio.1001277. Epub 2012 Mar 6. PMID: 22412349


8) Genome-wide studies highlight indirect links between human replication origins and gene regulation. Cadoret JC, Meisch F, Hassan-Zadeh V, Luyten I, Guillet C, Duret L, Quesneville H, Prioleau MN. Proc Natl Acad Sci U S A. 2008 Oct 14;105(41):15837-42. doi: 10.1073/pnas.0805208105. Epub 2008 Oct 6. PMID: 18838675


9) Broadening of DNA replication origin usage during metazoan cell differentiation. Dazy S, Gandrillon O, Hyrien O, Prioleau MN. EMBO Rep. 2006 Aug;7(8):806-11. doi: 10.1038/sj.embor.7400736. Epub 2006 Jun 16. PMID: 16799461


10) Replication of the chicken beta-globin locus: early-firing origins at the 5′ HS4 insulator and the rho- and betaA-globin genes show opposite epigenetic modifications. Prioleau MN, Gendron MC, Hyrien O. Mol Cell Biol. 2003 May;23(10):3536-49. doi: 10.1128/MCB.23.10.3536-3549.2003. PMID: 12724412