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Molecular and Cellular Biology, June 2004, p. 4801-4809, Vol. 24, No. 11
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.11.4801-4809.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Identification of a Distinctive Mutation Spectrum Associated with High Levels of Transcription in Yeast

Malcolm J. Lippert,^1* Jennifer A. Freedman,^2, Melissa A. Barber,^1, and Sue Jinks-Robertson^2,3

Department of Biology, Saint Michael's College, Colchester, Vermont 05439,¹ Graduate Program in Genetics and Molecular Biology,² Biology Department, Emory University, Atlanta, Georgia 30322³

Received 5 December 2003/ Returned for modification 29 December 2003/ Accepted 15 March 2004

High levels of transcription are associated with increased mutation rates in Saccharomyces cerevisiae, a phenomenon termed transcription-associated mutation (TAM). To obtain insight into the mechanism of TAM, we obtained LYS2 forward mutation spectra under low- versus high-transcription conditions in which LYS2 was expressed from either the low-level pLYS2 promoter or the strong pGAL1-10 promoter, respectively. Because of the large size of the LYS2 locus, forward mutations first were mapped to specific LYS2 subregions, and then those mutations that occurred within a defined 736-bp target region were sequenced. In the low-transcription strain base substitutions comprised the majority (64%) of mutations, whereas short insertion-deletion mutations predominated (56%) in the high-transcription strain. Most notably, deletions of 2 nucleotides (nt) comprised 21% of the mutations in the high-transcription strain, and these events occurred predominantly at 5'-(G/C)AAA-3' sites. No –2 events were present in the low-transcription spectrum, thus identifying 2-nt deletions as a unique mutational signature for TAM.

Present address: Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710.

Present address: Molecular and Cellular Biology Graduate Program, Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756.

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