title: Deciphering DNA replication dynamics in eukaryotic cell populations in relation with their averaged chromatin conformations.
abstract: We propose a non-local model of DNA replication that takes into account the observed uncertainty on the position and time of replication initiation in eukaryote cell populations. By picturing replication initiation as a two-state system and considering all possible transition configurations, and by taking into account the chromatin's fractal dimension, we derive an analytical expression for the rate of replication initiation. This model predicts with no free parameter the temporal profiles of initiation rate, replication fork density and fraction of replicated DNA, in quantitative agreement with corresponding experimental data from both S. cerevisiae and human cells and provides a quantitative estimate of initiation site redundancy. This study shows that, to a large extent, the program that regulates the dynamics of eukaryotic DNA replication is a collective phenomenon that emerges from the stochastic nature of replication origins initiation.
authors.affiliation: Ibitec-S, CEA, Gif-sur-Yvette, France.
authors.forename: A
authors.initials: A
authors.lastname: Goldar
authors.affiliation: Université de Lyon, F-69000 Lyon, France.|Laboratoire de Physique, Ecole Normale Supérieure de Lyon, CNRS UMR5672, F-69007 Lyon, France.
authors.forename: A
authors.initials: A
authors.lastname: Arneodo
authors.affiliation: Université de Lyon, F-69000 Lyon, France.|Laboratoire de Physique, Ecole Normale Supérieure de Lyon, CNRS UMR5672, F-69007 Lyon, France.
authors.forename: B
authors.initials: B
authors.lastname: Audit
authors.affiliation: Université de Lyon, F-69000 Lyon, France.|Laboratoire de Physique, Ecole Normale Supérieure de Lyon, CNRS UMR5672, F-69007 Lyon, France.
authors.forename: F
authors.initials: F
authors.lastname: Argoul
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS UMR8197, Inserm U1024, 75005 Paris, France.|Institut Pasteur, 75015 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Rappailles
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS UMR8197, Inserm U1024, 75005 Paris, France.|MRC Laboratory of Molecular Biology, Francis Crick Avenue, Cambridge, CB2 0QH, UK.
authors.forename: G
authors.initials: G
authors.lastname: Guilbaud
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS UMR8197, Inserm U1024, 75005 Paris, France.|Biotech Research and Innovation Centre (BRIC), University of Copenhagen, Ole Maaløes Vej 5, Copenhagen 2200, Denmark.
authors.forename: N
authors.initials: N
authors.lastname: Petryk
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS UMR8197, Inserm U1024, 75005 Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Kahli
authors.affiliation: Institut de Biologie de l'Ecole Normale Supérieure (IBENS) CNRS UMR8197, Inserm U1024, 75005 Paris, France.
authors.forename: O
authors.initials: O
authors.lastname: Hyrien
mesh_terms: D002460:Cell Line; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D004261:DNA Replication / Q000502:physiology*; D006801:Humans; D018741:Replication Origin / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin