title: The replicon revisited: an old model learns new tricks in metazoan chromosomes.
abstract: The origins of DNA replication were proposed in the replicon model to be specified genetically by replicator elements that coordinate the initiation of DNA synthesis with gene expression and cell growth. Recent studies have identified DNA sequences in mammalian cells that fulfil the genetic criteria for replicators and are beginning to uncover the sequence requirements for the initiation of DNA replication. Mammalian replicators are com- posed of non-redundant modules that cooperate to direct initiation to specific chromosomal sites. Conversely, replicators do not show strong sequence similarity, and their ability to initiate replication depends on the chromosomal context and epigenetic factors, as well as their primary sequence. Here, we review the properties of metazoan replicators, and discuss the genetic and epigenetic factors that determine where and when DNA replication is initiated.
authors.affiliation: Laboratory of Molecular Pharmacology, DSB, National Cancer Institute, National Institutes of Health, Building 37, Room 5056, 37 Convent Drive, Bethesda, Maryland 20892-4255, USA. aladjemm@mail.nih.gov
authors.forename: Mirit I
authors.initials: MI
authors.lastname: Aladjem
authors.forename: Ellen
authors.initials: E
authors.lastname: Fanning
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism; D002875:Chromosomes / Q000648:ultrastructure*; D018899:CpG Islands; D004247:DNA / Q000378:metabolism / Q000648:ultrastructure*; D019175:DNA Methylation; D004261:DNA Replication; D006801:Humans; D008957:Models, Genetic; D017434:Protein Structure, Tertiary; D018741:Replication Origin; D014158:Transcription, Genetic
chemical_list: D002843:Chromatin; D004247:DNA