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

Cell Rep. 2014 Jan 30;6(2):346-56. doi: 10.1016/j.celrep.2013.12.037. Epub 2014 Jan 16.

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 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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA Breaks
  • Genome, Fungal*
  • Genomic Instability*
  • Protein Binding
  • RecQ Helicases / genetics
  • RecQ Helicases / metabolism*
  • Saccharomyces cerevisiae / enzymology*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Telomere / genetics
  • Telomere / metabolism
  • Telomere Homeostasis

Substances

  • Saccharomyces cerevisiae Proteins
  • Hrq1 protein, S cerevisiae
  • RecQ Helicases