Structural basis for DNA duplex separation by a superfamily-2 helicase

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Abstract
To reveal the mechanism of processive strand separation by superfamily-2 (SF2) 3′→5′ helicases, we determined apo and DNA-bound crystal structures of archaeal Hel308, a helicase that unwinds lagging strands and is related to human DNA polymerase θ. Our structure captures the duplex-unwinding reaction, shows that initial strand separation does not require ATP and identifies a prominent β-hairpin loop as the unwinding element. Similar loops in hepatitis C virus NS3 helicase and RNA-decay factors support the idea that this duplex-unwinding mechanism is applicable to a broad subset of SF2 helicases. Comparison with ATP-bound SF2 enzymes suggests that ATP promotes processive unwinding of 1 base pair by ratchet-like transport of the 3′ product strand. Our results provide a first structural framework for strand separation by processive SF2 3′→5′ helicases and reveal important mechanistic differences from SF1 helicases.