Genetics, Vol. 154, 109-120, January 2000, Copyright © 2000

Genetic Analysis of Transcription-Associated Mutation in Saccharomyces cerevisiae

Natalie J. Moreya, Christopher N. Greenea, and Sue Jinks-Robertsona,b
a Graduate Program in Genetics and Molecular Biology, Emory University, Atlanta, Georgia 30322
b Department of Biology, Emory University, Atlanta, Georgia 30322

Corresponding author: Sue Jinks-Robertson, Department of Biology, Emory University, 1510 Clifton Rd., Atlanta, GA 30322., jinks{at}biology.emory.edu (E-mail)

Communicating editor: M. HAMPSEY

High levels of transcription are associated with elevated mutation rates in yeast, a phenomenon referred to as transcription-associated mutation (TAM). The transcription-associated increase in mutation rates was previously shown to be partially dependent on the Rev3p translesion bypass pathway, thus implicating DNA damage in TAM. In this study, we use reversion of a pGAL-driven lys2{Delta}Bgl allele to further examine the genetic requirements of TAM. We find that TAM is increased by disruption of the nucleotide excision repair or recombination pathways. In contrast, elimination of base excision repair components has only modest effects on TAM. In addition to the genetic studies, the lys2{Delta}Bgl reversion spectra of repair-proficient low and high transcription strains were obtained. In the low transcription spectrum, most of the frameshift events correspond to deletions of AT base pairs whereas in the high transcription strain, deletions of GC base pairs predominate. These results are discussed in terms of transcription and its role in DNA damage and repair.




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