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

ABSTRACT: 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.

SUBMITTER: Lemoine FJ

PROVIDER: S-EPMC2519721 | biostudies-literature | 2008 Sep

REPOSITORIES: biostudies-literature

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

Lemoine Francene J FJ Degtyareva Natasha P NP Kokoska Robert J RJ Petes Thomas D TD

Molecular and cellular biology 20080630 17

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 stu ...[more]

PMID: 18591249

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