Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN

Summary The RecQ family of DNA helicases including WRN ( W e rn er syndrome protein) and BLM ( Bl oo m syndrome protein) protects the genome against deleterious changes. Here we report the cocrystal structure of the R ec Q C -terminal (RQC) domain of human WRN bound to a DNA duplex. In the complex, the RQC domain specifically interacted with a blunt end of the duplex and, surprisingly, unpaired a Watson-Crick base pair in the absence of an ATPase domain. The β wing, an extended hairpin motif that is characteristic of winged-helix motifs, was used as a "separating knife" to wedge between the first and second base pairs, whereas the recognition helix, a principal component of helix-turn-helix motifs that are usually embedded within DNA grooves, was unprecedentedly excluded from the interaction. Our results demonstrate a function of the winged-helix motif central to the helicase reaction, establishing the first structural paradigm concerning the DNA structure-specific activities of the RecQ helicases.