title: Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.
abstract: In mammalian cells, perturbations in DNA replication result in chromosome breaks in regions termed "fragile sites." Using DNA microarrays, we mapped recombination events and chromosome rearrangements induced by reduced levels of the replicative DNA polymerase-α in the yeast Saccharomyces cerevisiae. We found that the recombination events were nonrandomly associated with a number of structural/sequence motifs that correlate with paused DNA replication forks, including replication-termination sites (TER sites) and binding sites for the helicase Rrm3p. The pattern of gene-conversion events associated with cross-overs suggests that most of the DNA lesions that initiate recombination between homologs are double-stranded DNA breaks induced during S or G2 of the cell cycle, in contrast to spontaneous recombination events that are initiated by double-stranded DNA breaks formed prior to replication. Low levels of DNA polymerase-α also induced very high rates of aneuploidy, as well as chromosome deletions and duplications. Most of the deletions and duplications had Ty retrotransposons at their breakpoints.
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Margaret
authors.initials: M
authors.lastname: Dominska
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.
authors.forename: Patricia W
authors.initials: PW
authors.lastname: Greenwell
authors.affiliation: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710 tom.petes@duke.edu.
authors.forename: Thomas D
authors.initials: TD
authors.lastname: Petes
mesh_terms: D002869:Chromosome Aberrations; D043283:Chromosome Fragile Sites / Q000235:genetics*; D002874:Chromosome Mapping / Q000379:methods; D004259:DNA-Directed DNA Polymerase / Q000378:metabolism; D016681:Genome, Fungal / Q000235:genetics*; D023281:Genomics / Q000379:methods; D019656:Loss of Heterozygosity; D046228:Microarray Analysis; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000235:genetics*
chemical_list: D004259:DNA-Directed DNA Polymerase
keywords: break-induced replication; loss of heterozygosity; mitotic cross-overs