A screen for synthetic genetic interactions with the Saccharomyces cerevisiae hrq1ΔN allele

The Saccharomyces cerevisiae Hrq1 helicase is a functional homolog of the disease-linked human RECQL4 enzyme and has been used as a model to study RecQ4 helicase subfamily biology. Although the motor cores of Hrq1 and RECQL4 are quite similar, these proteins display distinct N-terminal domains (NTDs) of unknown function. Do these domains facilitate species-specific activities by the two helicases, or do they serve common roles despite their differences in sequence and predicted structure? We probed these questions here by analyzing an NTD-truncated isoform of Hrq1 (Hrq1ΔN) both in vitro and in vivo. We found that the Hrq1 NTD houses a cryptic DNA binding site and that the hrq1ΔN allele is distinct from both hrq1Δ and the catalytically inactive hrq1-K318A mutant. Using synthetic genetic array analysis of hrq1ΔN crossed to the yeast S. cerevisiae single-gene deletion and temperature-sensitive allele collections, we also identified hundreds of synthetic genetic interactions. As with similar analyses of hrq1Δ and hrq1-K318A, our results suggest roles for Hrq1 and its NTD in multiple physiological pathways that underpin genome integrity. Together, these data are guiding our ongoing efforts to understand the roles of Hrq1 and RECQL4 in genome maintenance, which will help to explain why RECQL4 mutations cause disease.