title: Genetic and epigenetic determinants of DNA replication origins, position and activation.
abstract: In the genome of eukaryotic cells, DNA synthesis is initiated at multiple sites called origins of DNA replication. Origins must fire only once per cell cycle and how this is achieved is now well understood. However, little is known about the mechanisms that determine when and where replication initiates in a given cell. A large body of evidence indicates that origins are not equal in terms of efficiency and timing of activation. Origin usage also changes concomitantly with the different cell differentiation programs. As DNA replication occurs in the context of chromatin, initiation could be influenced by multiple parameters, such as nucleosome positioning, histone modifications, and three-dimensional (3D) organization of the nucleus. This view is supported by recent genome-wide studies showing that DNA replication profiles are shaped by genetic and epigenetic processes that act both at the local and global levels to regulate origin function in eukaryotic cells.
authors.affiliation: Institute of Human Genetics, 141 rue de la Cardonille, 34396 Montpellier Cedex 5, France. mechali@igh.cnrs.fr
authors.forename: Marcel
authors.initials: M
authors.lastname: Méchali
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Yoshida
authors.forename: Philippe
authors.initials: P
authors.lastname: Coulombe
authors.forename: Philippe
authors.initials: P
authors.lastname: Pasero
mesh_terms: D002453:Cell Cycle; D002843:Chromatin / Q000235:genetics; D004261:DNA Replication / Q000235:genetics*; D044127:Epigenesis, Genetic / Q000235:genetics*; D056890:Eukaryota / Q000235:genetics*; D016678:Genome; D006801:Humans; D009707:Nucleosomes / Q000235:genetics; D018741:Replication Origin / Q000235:genetics*; D012093:Replicon / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism
chemical_list: D002843:Chromatin; D009707:Nucleosomes