Comprehensive synthetic genetic array analysis of alleles that interact with mutation of theSaccharomyces cerevisiaeRecQ helicases Hrq1 and Sgs1

Most eukaryotic genomes encode multiple RecQ family helicases, including five such enzymes in humans. For many years, the yeastSaccharomyces cerevisiaewas considered unusual in that it only contained a single RecQ helicase, named Sgs1. However, it has recently been discovered that a second RecQ helicase, called Hrq1, resides in yeast. Both Hrq1 and Sgs1 are involved in genome integrity, functioning in processes such as DNA inter-strand crosslink repair, double-strand break repair, and telomere maintenance. However, it is unknown if these enzymes interact at a genetic, physical, or functional level as demonstrated for their human homologs. Thus, we performed synthetic genetic array (SGA) analyses ofhrq1Δandsgs1Δmutants. As inactive alleles of helicases can demonstrate dominant phenotypes, we also performed SGA analyses on thehrq1-K318Aandsgs1-K706AATPase/helicase-null mutants, as well as all combinations of deletion and inactive double mutants. We crossed these eight query strains (hrq1Δ, sgs1Δ, hrq1-K318A, sgs1-K706A, hrq1Δ sgs1Δ, hrq1Δ sgs1-K706A, hrq1-K318A sgs1Δ, andhrq1-K318A sgsl-K706A) to theS. cerevisiaesingle gene deletion and temperature-sensitive allele collections to generate double and triple mutants and scored them for synthetic positive and negative genetic effects based on colony growth. These screens identified hundreds of synthetic interactions, supporting the known roles of Hrq1 and Sgs1 in DNA repair, as well as suggesting novel connections to rRNA processing, mitochondrial DNA maintenance, transcription, and lagging strand synthesis during DNA replication.