The conserved SEN1 DNA:RNA helicase has multiple functions during yeast meiosis

Diploid Saccharomyces cerevisiae cells undergo meiosis when they are starved of nitrogen in the presence of a non-fermentable carbon source. Nutrient starvation triggers expression of Ime1, a master regulatory protein required to activate transcription of meiotic “early genes” that mediate premeiotic S phase and prophase I processes, including recombination and chromosome synapsis. During prophase I, the highly conserved, toposomerase-like protein, Spo11, creates double strand breaks that are used to identify homologous chromosomes and generate crossovers between them. DNA:RNA hybrids are formed when an RNA molecule anneals to a complementary strand of DNA and are present at the ends of double strand breaks during prophase I of meiosis in a variety of organisms. DNA:RNA hybrids can be removed by degradation of the RNA by RNase H or by unwinding of the RNA by an essential, multi-functional DNA:RNA helicase called Sen1. Sen1 is orthologous to the mammalian Senataxin ( SETX ) helicase. Phenotypic characterization of mouse mutants lacking either Senataxin or RNase H activity exhibit male infertility and defects in double strand break repair. SETX is also required for meiotic sex chromosome inactivation, making it unclear whether SETX ’s role in meiotic recombination is direct or an indirect consequence due to defects in SETX functions that affect transcription. Using a variety of orthogonal approaches, this work demonstrates that SEN1 has multiple, temporally distinct roles that promote yeast meiosis. First, it enables the timely expression of IME1 -regulated early genes. Second, it helps prevent and/or remove DNA:RNA hybrids that form during premeiotic S phase. Third, it facilitates both repair of Spo11 generated double strand breaks generated during prophase I and chromosome synapsis.