Modulation of UV-induced mutagenesis in budding yeast, Saccharomyces cerevisiae

초록

Cellular mutation rate is increased by exposure to DNA damaging agents. In yeast, ultra violet (UV) light induces mutagenesis increase in dose-dependent manner in wildtype. UV-induced mutagenesis is drastically elevated in DNA repair deficient mutants. Previously, we reported that yeast RAD2, a nucleotide excision repair (NER) related gene, functions in transcription elongation, and that defects of the genes cause increased spontaneous and MMS-induced mutagenesis. In this study, we demonstrated the requirement for SPT4, a gene encoding NER-independent transcription elongation factor, in cell growth along with its role in mutagenesis in both the presence and absence of DNA damage. We found that SPT4 expression is increased when a NER-related transcription elongation factor is defective. SPT4 appeared to promote transcription elongation across DNA lesions, thereby increasing the cell survival rate in exchange for increased mutagenesis. Further, our results might explain the decrease in mutant Huntingtin protein in neuronal cells upon inhibition of Supt4, the mammalian ortholog of yeast Spt4p. [연구비과제번호: 20090071325〕 Key words: DNA damaging agents, DNA repair, Mutagenesis