Genome-wide high-resolution mapping of chromosome fragile sites in Saccharomyces cerevisiae.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Song, W; Dominska, M; Greenwell, PW; Petes, TD

Published Date

  • May 27, 2014

Published In

Volume / Issue

  • 111 / 21

Start / End Page

  • E2210 - E2218

PubMed ID

  • 24799712

Pubmed Central ID

  • 24799712

Electronic International Standard Serial Number (EISSN)

  • 1091-6490

Digital Object Identifier (DOI)

  • 10.1073/pnas.1406847111

Language

  • eng

Conference Location

  • United States