title: Eukaryotic replication origins: Strength in flexibility.
abstract: The eukaryotic replicative DNA helicase, Mcm2-7, is loaded in inactive form as a double hexameric complex around double-stranded DNA. To ensure that replication origins fire no more than once per S phase, activation of the Mcm2-7 helicase is temporally separated from Mcm2-7 loading in the cell cycle. This 2-step mechanism requires that inactive Mcm2-7 complexes be maintained for variable periods of time in a topologically bound state on chromatin, which may create a steric obstacle to other DNA transactions. We have recently found in the budding yeast, Saccharomyces cerevisiae, that Mcm2-7 double hexamers can respond to collisions with transcription complexes by sliding along the DNA template. Importantly, Mcm2-7 double hexamers remain functional after displacement along DNA and support replication initiation from sites distal to the origin. These results reveal a novel mechanism to specify eukaryotic replication origin sites and to maintain replication origin competence without the need for Mcm2-7 reloading.
authors.affiliation: a Molecular Biology Program, Memorial Sloan-Kettering Cancer Center , New York , NY , USA.
authors.forename: Charanya
authors.initials: C
authors.lastname: Kumar
authors.affiliation: a Molecular Biology Program, Memorial Sloan-Kettering Cancer Center , New York , NY , USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Remus
mesh_terms: D000818:Animals; D004247:DNA / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004789:Enzyme Activation; D056890:Eukaryota / Q000235:genetics*; D006801:Humans; D064110:Minichromosome Maintenance Proteins / Q000378:metabolism; D018741:Replication Origin; D014158:Transcription, Genetic
chemical_list: D004247:DNA; D064110:Minichromosome Maintenance Proteins
keywords: DNA replication; Mcm2-7; ORC; chromosomes; replication origin