Hrq1, a Homolog of the Human RecQ4 Helicase, Acts Catalytically and Structurally to Promote Genome Integrity

•Hrq1 is a functional homolog of hRecQ4•Purified Hrq1 is a potent in vitro helicase and forms heptameric rings•Hrq1 acts catalytically to protect against DNA interstrand crosslinks•Hrq1 has many telomere roles, e.g., noncatalytic suppression of telomere addition

SummaryHuman RecQ4 (hRecQ4) affects cancer and aging but is difficult to study because it is a fusion between a helicase and an essential replication factor. Budding yeast Hrq1 is homologous to the disease-linked helicase domain of RecQ4 and, like hRecQ4, is a robust 3′-5′ helicase. Additionally, Hrq1 has the unusual property of forming heptameric rings. Cells lacking Hrq1 exhibited two DNA damage phenotypes: hypersensitivity to DNA interstrand crosslinks (ICLs) and telomere addition to DNA breaks. Both activities are rare; their coexistence in a single protein is unprecedented. Resistance to ICLs requires helicase activity, but suppression of telomere addition does not. Hrq1 also affects telomere length by a noncatalytic mechanism, as well as telomerase-independent telomere maintenance. Because Hrq1 binds telomeres in vivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to a role in ICL repair and/or suppression of de novo telomere addition.

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