A New Hyperrecombination Mutation Identifies a Novel Yeast Gene, THP1, Connecting Transcription Elongation With Mitotic Recombination

Corresponding author: Andrés Aguilera, Departamento de Genética, Facultad de Biología, Universidad de Sevilla, Avd. Reina Mercedes 6, 41012 Seville, Spain., aguilo{at}cica.es (E-mail)

Communicating editor: L. S. SYMINGTON

Given the importance of the incidence of recombination in genomic instability, it is of great interest to know the elements or processes controlling recombination in mitosis. One such process is transcription, which has been shown to induce recombination in bacteria, yeast, and mammals. To further investigate the genetic control of the incidence of recombination and genetic instability and, in particular, its connection with transcription, we have undertaken a search for hyperrecombination mutants among a large number of strains deleted in genes of unknown function. We have identified a new gene, THP1 (YOL072w), whose deletion mutation strongly stimulates recombination between repeats. In addition, thp1 impairs transcription, a defect that is particularly strong at the level of elongation through particular DNA sequences such as lacZ. The hyperrecombination phenotype of thp1 cells is fully dependent on transcription elongation of the repeat construct. When transcription is impeded either by shutting off the promoter or by using a premature transcription terminator, hyperrecombination between repeats is abolished, 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 recombination, Hpr1p and Tho2p, act in the same "pathway" connecting transcription elongation with the incidence of mitotic recombination.

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