Genetic analysis of transcription-associated mutation in Saccharomyces cerevisiae

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 sh own 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-d riven 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 bass excisio n repair components I-las only modest effects on TAM. In addition to the ge netic studies, the lys2 Delta Bgl reversion spectra of repair-proficient lo w and high transcription strains were obtained. In the low transcription sp ectrum, most of the frameshift events correspond to deletions of AT base pa irs whereas in the high transcription strain, deletions of GC base pairs pr edominate. These results are discussed in terms of transcription and its ro le in DNA damage and repair.