AI Article Synopsis
- Specific regions of genomes, known as fragile sites, are prone to chromosome rearrangements linked to various cancers, highlighting the importance of studying their stability.
- Researchers identified two fragile sites in the yeast Saccharomyces cerevisiae that become unstable when Pol1p, a key DNA polymerase alpha component, is expressed at lower levels.
- The study finds that reduced levels of another DNA polymerase, Pol3p (DNA polymerase delta), also destabilize these sites, causing chromosomal abnormalities, indicating that changes in DNA polymerase levels can lead to harmful DNA breaks.
Article 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.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2519721 | PMC |
| http://dx.doi.org/10.1128/MCB.02084-07 | DOI Listing |
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