title: DNA replication origins-where do we begin?
abstract: For more than three decades, investigators have sought to identify the precise locations where DNA replication initiates in mammalian genomes. The development of molecular and biochemical approaches to identify start sites of DNA replication (origins) based on the presence of defining and characteristic replication intermediates at specific loci led to the identification of only a handful of mammalian replication origins. The limited number of identified origins prevented a comprehensive and exhaustive search for conserved genomic features that were capable of specifying origins of DNA replication. More recently, the adaptation of origin-mapping assays to genome-wide approaches has led to the identification of tens of thousands of replication origins throughout mammalian genomes, providing an unprecedented opportunity to identify both genetic and epigenetic features that define and regulate their distribution and utilization. Here we summarize recent advances in our understanding of how primary sequence, chromatin environment, and nuclear architecture contribute to the dynamic selection and activation of replication origins across diverse cell types and developmental stages.
authors.affiliation: Institut Jacques Monod, UMR7592, Centre National de la Recherche Scientifique, Universite Paris Diderot, Equipe Labellisee Association pour la Recherche sur le Cancer, Paris 75013, France;
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Prioleau
authors.affiliation: Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710. USA.
authors.forename: David M
authors.initials: DM
authors.lastname: MacAlpine
mesh_terms: D000818:Animals; D004261:DNA Replication / Q000235:genetics*; D008322:Mammals; D018741:Replication Origin / Q000235:genetics*
keywords: DNA replication; chromatin; epigenetics; nuclear architecture; origins of DNA replication