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Molecular and Cellular Biology, September 2008, p. 5359-5368, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.02084-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Reduced Levels of DNA Polymerase Induce Chromosome Fragile Site Instability in Yeast ^,

Francene J. Lemoine,^1,* Natasha P. Degtyareva,^1,, Robert J. Kokoska,² and Thomas D. Petes¹

Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710,¹ Life Sciences Division, U.S. Army Research Office, Research Triangle Park, North Carolina 27709-2211²

Received 20 November 2007/ Returned for modification 8 January 2008/ Accepted 16 June 2008

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 . In the study presented here, we show that reduced levels of Pol3p, the catalytic subunit of DNA polymerase , 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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* Corresponding author. Present address: Department of Biological Sciences, Northwestern State University of Louisiana, Natchitoches, LA 71497. Phone: (318) 357-5805. Fax: (318) 357-4518. E-mail: lemoinef{at}nsula.edu

Published ahead of print on 30 June 2008.

Supplemental material for this article may be found at http://mcb.asm.org/.

Contributed equally to the research.

Present address: Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322.

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Molecular and Cellular Biology, September 2008, p. 5359-5368, Vol. 28, No. 17
0270-7306/08/$08.00+0     doi:10.1128/MCB.02084-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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