DNA damage activates transcription and transposition of yeast Ty retrotransposons

Abstract

A set of genes isolated from Saccharomyces cerevisiae showed increased transcript levels after yeast had been exposed to ultraviolet (UV) light or 4-nitroquinoline-1-oxide (4NQO). Included among these DNA damage responsive (DDR) genes were members of the Ty retrotransposon family of yeast. Northern hybridization analysis indicated that maximal levels of a 5.6 kb transcript encoded by the Ty elements accumulated in cells after 4 to 6 h of exposure to 4NQO. The induced levels of transcripts varied from two- to tenfold for different Ty probes although similar kinetics and dose responses were observed for transcripts hybridizing to the different Ty family members. Pulse labeling experiments suggested that the accumulation of Ty transcripts was due, in part, to an increased rate of Ty message synthesis. Transposition of Ty elements to two target loci encoding distinct alcohol dehydrogenase enzymes, ADH2 and ADH4, was examined in cells exposed to increasing doses of UV light or 4NQO. The frequency of Ty insertion into these genetic regions following DNA damaging treatments increased by as much as 17-fold compared with untreated cells. These results provide direct evidence that transposable elements can be activated by physical and chemical mutagens/carcinogens and that transpositional mutagenesis is induced by these agents in S. cerevisiae.