Hrq1, a homolog of the human RecQ4 helicase, acts catalytically and structurally to promote genome integrity.
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.
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA. Electronic address: bochman@indiana.edu.
Matthew L
ML
Bochman
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Katrin
K
Paeschke
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Angela
A
Chan
Department of Molecular Biology, Princeton University, Princeton, NJ 08544, USA.
Virginia A
VA
Zakian
D053960:DNA Breaks; D016681:Genome, Fungal; D042822:Genomic Instability; D011485:Protein Binding; D053484:RecQ Helicases / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D016615:Telomere / Q000235:genetics / Q000378:metabolism; D059505:Telomere Homeostasis
D029701:Saccharomyces cerevisiae Proteins; C579040:Hrq1 protein, S cerevisiae; D053484:RecQ Helicases