A new hyperrecombination mutation identifies a novel yeast gene, THP1, connecting transcription elongation with mitotic recombination

Given the importance the incidence of recombination in genomic instability, it is of great interest to know the elements or processes controlling reco mbination in mitosis. One such process is transcription, which has been sho wn to induce rccombination in bacteria, yeast, and mammals. To further inve stigate the genetic control of the incidence of recombination and genetic i nstability and, in particular- its connection with transcription, we have u ndertaken a search for hypercombination mutans among a large number of stra ins deleted in genes of unknown function. We have identified a new gene, TH P1 (YOL072w), whose deletion mutation strongly stimulates recombination bet ween repeats In addition, thp1 Delta impairs transcription a defect that is particularly strong at the level of elongation through particular DNA sequ ences such as lacZ The hypercombination phenotype of thp1 Delta cells is fu lly dependent on transcription elongation of the repeat construct. When tra nscription is impeded either by shutting off the promoter or by using a pre mature transcription terminator, hyperrccombination between repeats is abol ished, providing new evidence that transcription-elongation impairment may be a source of recombinogenic substrates in mitosis. We show that Thp1p and two other proteins previously shown to control transcription-associated re combination, Hpr1p, and Tho2p, act in the same "pathway " connecting transc ription elongation with the incidence of mitotic recombination.