Human RECQ1 helicase-driven DNA unwinding, annealing, and branch migration: Insights from DNA complex structures

• DOI: 10.1073/pnas.1417594112
• Publication Date: 2015-03-24T03:17:43Z
• Authors: Ashley C. W. Pike; Shivasankari Goma...; Paolo Swuec; Matteo Berti; Ying Zhang; Christina Schnecke; Francesca Marino; Frank von Delft; Ludovic Renault; Alessandro Costa; Opher Gileadi; Alessandro Vindigni
• Keywords: Insecta; Molecular Conformation; DNA, Single-Stranded; DNA helicases; Crystallography, X-Ray; Nucleic Acid Denaturation; fork reversal; 03 medical and health sciences; RecQ; Escherichia coli; Animals; Humans; DNA, Cruciform; 0303 health sciences; RecQ Helicases; Nucleotides; DNA Helicases; Holliday junction; DNA helicases; Fork reversal; Genome stability; Holliday junction; RecQm; Animals; Chromatography, Gel; Crystallization; Crystallography, X-Ray; DNA; DNA Helicases; DNA, Cruciform; DNA, Single-Stranded; Escherichia coli; Humans; Insecta; Molecular Conformation; Nucleic Acid Denaturation; Nucleotides; Protein Binding; Protein Structure, Tertiary; RecQ Helicases; Zinc; Multidisciplinary; DNA; Protein Structure, Tertiary; Zinc; Chromatography, Gel; Crystallization; genome stability; Protein Binding

Significance RecQ DNA helicases are critical enzymes for the maintenance of genome integrity. Here, we determined the first DNA complex structures, to our knowledge, of the human RECQ1 helicase. These structures provide new insight into the RecQ helicase mechanism of DNA tracking, strand separation, strand annealing, and Holliday junction (HJ) branch migration. We identified a surface region in the winged-helix domain of RECQ1 that is important for both dsDNA recognition and HJ resolution, and we used a combination of biochemical, analytical ultracentrifugation, and EM experiments to begin elucidating the molecular basis of the distinct HJ resolution activities of human RecQ helicases.