Yeast Hrq1 shares structural and functional homology with the disease-linked human RecQ4 helicase.
The five human RecQ helicases participate in multiple processes required to maintain genome integrity. Of these, the disease-linked RecQ4 is the least studied because it poses many technical challenges. We previously demonstrated that the yeast Hrq1 helicase displays similar functions to RecQ4 in vivo, and here, we report the biochemical and structural characterization of these enzymes. In vitro, Hrq1 and RecQ4 are DNA-stimulated ATPases and robust helicases. Further, these activities were sensitive to DNA sequence and structure, with the helicases preferentially unwinding D-loops. Consistent with their roles at telomeres, telomeric repeat sequence DNA also stimulated binding and unwinding by these enzymes. Finally, electron microscopy revealed that Hrq1 and RecQ4 share similar structural features. These results solidify Hrq1 as a true RecQ4 homolog and position it as the premier model to determine how RecQ4 mutations lead to genomic instability and disease.
Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA.
Cody M
CM
Rogers
Electron Microscopy Center, Indiana University, Bloomington, IN 47405, USA.
Joseph Che-Yen
JC
Wang
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Hiroki
H
Noguchi
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Tsuyoshi
T
Imasaki
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Yuichiro
Y
Takagi
Molecular and Cellular Biochemistry Department, Indiana University, Bloomington, IN 47405, USA.
Matthew L
ML
Bochman
D004247:DNA / Q000378:metabolism; D004260:DNA Repair; D004194:Disease / Q000235:genetics*; D005822:Genetic Vectors / Q000378:metabolism; D006801:Humans; D007700:Kinetics; D009690:Nucleic Acid Conformation; D053484:RecQ Helicases / Q000737:chemistry* / Q000378:metabolism*; D012091:Repetitive Sequences, Nucleic Acid / Q000235:genetics; D012441:Saccharomyces cerevisiae / Q000201:enzymology* / Q000235:genetics / Q000648:ultrastructure; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry* / Q000378:metabolism*; D040681:Structural Homology, Protein; D013379:Substrate Specificity; D016615:Telomere / Q000235:genetics
D029701:Saccharomyces cerevisiae Proteins; D004247:DNA; C579040:Hrq1 protein, S cerevisiae; D053484:RecQ Helicases