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 that is likely important for DNA repair because the hrq1ΔN allele phenocopies the DNA inter-strand crosslink sensitivity of hrq1Δ . 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, many of which are shared with previously characterized hrq1 mutants. 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.

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Journal Article

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Shumaker KA, Kumcu ME, McDevitt FE, Rogers CM, Bochman ML

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