Identification of a distinctive mutation spectrum associated with high levels of transcription in yeast.

Journal Article (Journal Article)

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.

Full Text

Duke Authors

Cited Authors

  • Lippert, MJ; Freedman, JA; Barber, MA; Jinks-Robertson, S

Published Date

  • June 2004

Published In

Volume / Issue

  • 24 / 11

Start / End Page

  • 4801 - 4809

PubMed ID

  • 15143174

Pubmed Central ID

  • PMC416428

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/MCB.24.11.4801-4809.2004


  • eng

Conference Location

  • United States