Reduced levels of DNA polymerase delta induce chromosome fragile site instability in yeast

Mol Cell Biol. 2008 Sep;28(17):5359-68. doi: 10.1128/MCB.02084-07. Epub 2008 Jun 30.


Specific regions of genomes (fragile sites) are hot spots for the chromosome rearrangements that are associated with many types of cancer cells. Understanding the molecular mechanisms regulating the stability of chromosome fragile sites, therefore, has important implications in cancer biology. We previously identified two chromosome fragile sites in Saccharomyces cerevisiae that were induced in response to the reduced expression of Pol1p, the catalytic subunit of DNA polymerase alpha. In the study presented here, we show that reduced levels of Pol3p, the catalytic subunit of DNA polymerase delta, induce instability at these same sites and lead to the generation of a variety of chromosomal aberrations. These findings demonstrate that a change in the stoichiometry of replicative DNA polymerases results in recombinogenic DNA lesions, presumably double-strand DNA breaks.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Chromosome Fragile Sites*
  • Chromosome Fragility*
  • Chromosomes, Fungal / metabolism
  • Crosses, Genetic
  • DNA Damage
  • DNA Polymerase III / metabolism*
  • Diploidy
  • Gene Deletion
  • Genes, Fungal
  • Haploidy
  • Mitosis / drug effects
  • Molecular Sequence Data
  • Mutation / genetics
  • Nucleic Acid Hybridization
  • Phenotype
  • Recombination, Genetic / genetics
  • Reproduction
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*


  • POL3 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • DNA Polymerase III