title: Identification of mutations that decrease the stability of a fragment of Saccharomyces cerevisiae chromosome III lacking efficient replicators.
abstract: Eukaryotic chromosomes are duplicated during S phase and transmitted to progeny during mitosis with high fidelity. Chromosome duplication is controlled at the level of replication initiation, which occurs at cis-acting replicator sequences that are spaced at intervals of approximately 40 kb along the chromosomes of the budding yeast Saccharomyces cerevisiae. Surprisingly, we found that derivatives of yeast chromosome III that lack known replicators were replicated and segregated properly in at least 96% of cell divisions. To gain insight into the mechanisms that maintain these "originless" chromosome fragments, we screened for mutants defective in the maintenance of an "originless" chromosome fragment, but proficient in the maintenance of the same fragment that carries its normal complement of replicators (originless fragment maintenance mutants, or ofm). We show that three of these Ofm mutations appear to disrupt different processes involved in chromosome transmission. The OFM1-1 mutant seems to disrupt an alternative initiation mechanism, and the ofm6 mutant appears to be defective in replication fork progression. ofm14 is an allele of RAD9, which is required for the activation of the DNA damage checkpoint, suggesting that this checkpoint plays a key role in the maintenance of the "originless" fragment.
authors.affiliation: Department of Microbiology and Molecular Genetics, UMDNJ-New Jersey Medical School, Newark, New Jersey 07103, USA.
authors.forename: James F
authors.initials: JF
authors.lastname: Theis
authors.forename: Ann
authors.initials: A
authors.lastname: Dershowitz
authors.forename: Carmela
authors.initials: C
authors.lastname: Irene
authors.forename: Clelia
authors.initials: C
authors.lastname: Maciariello
authors.forename: Michael L
authors.initials: ML
authors.lastname: Tobin
authors.forename: Giordano
authors.initials: G
authors.lastname: Liberi
authors.forename: Sahba
authors.initials: S
authors.lastname: Tabrizifard
authors.forename: Malgorzata
authors.initials: M
authors.lastname: Korus
authors.forename: Lucia
authors.initials: L
authors.lastname: Fabiani
authors.forename: Carol S
authors.initials: CS
authors.lastname: Newlon
mesh_terms: D000483:Alleles; D018797:Cell Cycle Proteins / Q000235:genetics; D043171:Chromosomal Instability; D015825:Chromosomes, Fungal / Q000235:genetics*; D004249:DNA Damage; D004261:DNA Replication / Q000235:genetics; D004271:DNA, Fungal / Q000096:biosynthesis / Q000235:genetics; D005800:Genes, Fungal; D009154:Mutation; D010641:Phenotype; D018741:Replication Origin; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics* / Q000378:metabolism / Q000528:radiation effects
chemical_list: D018797:Cell Cycle Proteins; D004271:DNA, Fungal; C069930:rad9 protein