title: How dormant origins promote complete genome replication.
abstract: Many replication origins that are licensed by loading MCM2-7 complexes in G1 are not normally used. Activation of these dormant origins during S phase provides a first line of defence for the genome if replication is inhibited. When replication forks fail, dormant origins are activated within regions of the genome currently engaged in replication. At the same time, DNA damage-response kinases activated by the stalled forks preferentially suppress the assembly of new replication factories, thereby ensuring that chromosomal regions experiencing replicative stress complete synthesis before new regions of the genome are replicated. Mice expressing reduced levels of MCM2-7 have fewer dormant origins, are cancer-prone and are genetically unstable, demonstrating the importance of dormant origins for preserving genome integrity. We review the function of dormant origins, the molecular mechanism of their regulation and their physiological implications.
authors.affiliation: Wellcome Trust Centre for Gene Regulation & Expression, University of Dundee Dow Street, Dundee DD1 5EH, UK. j.j.blow@dundee.ac.uk
authors.forename: J Julian
authors.initials: JJ
authors.lastname: Blow
authors.forename: Xin Quan
authors.initials: XQ
authors.lastname: Ge
authors.forename: Dean A
authors.initials: DA
authors.lastname: Jackson
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D016147:Genes, Tumor Suppressor; D051379:Mice; D064111:Minichromosome Maintenance Complex Component 2; D064126:Minichromosome Maintenance Complex Component 3; D064148:Minichromosome Maintenance Complex Component 4; D064151:Minichromosome Maintenance Complex Component 6; D064168:Minichromosome Maintenance Complex Component 7; D009687:Nuclear Proteins / Q000235:genetics*; D018741:Replication Origin / Q000235:genetics*; D016196:S Phase / Q000235:genetics; D037941:Silencer Elements, Transcriptional / Q000235:genetics*; D013269:Stochastic Processes
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; C489423:MCM5 protein, human; C513269:Mcm3 protein, mouse; D009687:Nuclear Proteins; C084859:MCM2 protein, human; C099243:MCM4 protein, human; C103258:MCM6 protein, human; C101624:MCM7 protein, human; D064111:Minichromosome Maintenance Complex Component 2; D064126:Minichromosome Maintenance Complex Component 3; D064148:Minichromosome Maintenance Complex Component 4; D064151:Minichromosome Maintenance Complex Component 6; D064168:Minichromosome Maintenance Complex Component 7