title: The temporal program of chromosome replication: genomewide replication in clb5{Delta} Saccharomyces cerevisiae.
abstract: Temporal regulation of origin activation is widely thought to explain the pattern of early- and late-replicating domains in the Saccharomyces cerevisiae genome. Recently, single-molecule analysis of replication suggested that stochastic processes acting on origins with different probabilities of activation could generate the observed kinetics of replication without requiring an underlying temporal order. To distinguish between these possibilities, we examined a clb5Delta strain, where origin firing is largely limited to the first half of S phase, to ask whether all origins nonspecifically show decreased firing (as expected for disordered firing) or if only some origins ("late" origins) are affected. Approximately half the origins in the mutant genome show delayed replication while the remainder replicate largely on time. The delayed regions can encompass hundreds of kilobases and generally correspond to regions that replicate late in wild-type cells. Kinetic analysis of replication in wild-type cells reveals broad windows of origin firing for both early and late origins. Our results are consistent with a temporal model in which origins can show some heterogeneity in both time and probability of origin firing, but clustering of temporally like origins nevertheless yields a genome that is organized into blocks showing different replication times.
authors.affiliation: Department of Genomic Resources, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
authors.forename: Heather J
authors.initials: HJ
authors.lastname: McCune
authors.forename: Laura S
authors.initials: LS
authors.lastname: Danielson
authors.forename: Gina M
authors.initials: GM
authors.lastname: Alvino
authors.forename: David
authors.initials: D
authors.lastname: Collingwood
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Delrow
authors.forename: Walton L
authors.initials: WL
authors.lastname: Fangman
authors.forename: Bonita J
authors.initials: BJ
authors.lastname: Brewer
authors.forename: M K
authors.initials: MK
authors.lastname: Raghuraman
mesh_terms: D015825:Chromosomes, Fungal / Q000235:genetics*; D019926:Cyclin B / Q000235:genetics* / Q000378:metabolism; D004261:DNA Replication; D004271:DNA, Fungal / Q000235:genetics / Q000378:metabolism; D016681:Genome, Fungal; D008957:Models, Genetic; D009154:Mutation; D016196:S Phase; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C076558:CLB5 protein, S cerevisiae; C095227:CLB6 protein, S cerevisiae; D019926:Cyclin B; D004271:DNA, Fungal; D029701:Saccharomyces cerevisiae Proteins