A reduction in RNA polymerase II initiation rate suppresses hyper-recombination and transcription-elongation impairment of THO mutants.

Hrs1/Med3, a component of the Mediator involved in transcription initiation, was previously isolated as a suppressor of hpr1Delta hyper-recombination linked to transcription elongation. Here we show that hrs1Delta-mediated suppression is specific of transcription-associated hyper-recombination (TAR). The decrease in recombination associated with hrs1Delta, either in wild-type or hpr1Delta cells is only observed in DNA repeats constructs in which transcription is Hrs1-dependent. We propose that the suppression of THO mutants by hrs1Delta is due to the specific effect of hrs1Delta on transcription initiation of the recombination system. In parallel we show that the higher the transcription of a gene the more important becomes the THO complex for its expression, implying that the in vivo relevance of this complex is dependent on the frequency of RNAPII transcription initiation. This study furthers the understanding of the importance of THO in transcription and the maintenance of genome stability.