The yeast HPR1 gene has a functional role in transcriptional elongation that uncovers a novel source of genome instability

Abstract

The yeast HPR1 gene plays an important role in genome stability, as indicated by the observation that hpr1 mutants have high frequencies of DNA repeat recombination and chromosome loss. Here we report that HPR1 is required for transcriptional elongation. Transcription driven from constitutive and regulated yeast promoters cannot elongate through the bacterial lacZ coding region in hpr1Δ cells, but progresses efficiently through other sequences such as yeast PHO5. We show that HPR1 is not required for transcription activation and that the previously reported effects of hpr1Δon the activation of different promoters is a consequence of the incapacity of hpr1Δ cells to elongate transcription through lacZ, used as reporter. Transcriptional defects are also observed in yeast DNA sequences ofhpr1Δ cells in the presence of the transcription elongation inhibitor 6-azauracil. In all cases, the blockage of transcription elongation inhpr1Δ is associated with both the high frequency of deletions and the increase in plasmid instability that we report here. Therefore, in addition to the identification of a new element involved in transcriptional elongation, our work provides evidence for a new source of genomic instability.