Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity

Matthew L. Bochman, Katrin Paeschke, Angela Chan, Virginia A. Zakian

Research output: Contribution to journalArticle

22 Scopus citations

Abstract

Human 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 invivo, it probably affects them directly. Thus, the tumor-suppressing activity of RecQ4 could be due to arole in ICL repair and/or suppression of de novo telomere addition.

Original languageEnglish (US)
Pages (from-to)346-356
Number of pages11
JournalCell Reports
Volume6
Issue number2
DOIs
StatePublished - 2014

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)

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