Archaeal Hel308 helicase targets replication forks in vivo and in vitro and unwinds lagging strands

Mutations in mammalian and Drosophila HeI308 and PoIQ paralogues cause genome instability but their helicase functions are mysterious. By in vivo and in vitro analysis, we show that HeI308 from archaea (HeI308a) may act at stalled replication forks. Introducing hel308a into Escherichia coli dnaE strains that conditionally accumulate stalled forks caused synthetic lethality, an effect indistinguishable from E.coli RecQ. Further analysis in vivo indicated that the effect of heI308a is exerted independently of homologous recombination. The minimal biochemical properties of HeI308a protein were the same as human HeI308. We describe how helicase actions of HeI308a at fork structures lead specifically to displacement of lagging strands. The invading strand of D-loops is also targeted. Using archaeal HeI308, we propose models of action for the helicase domain of PoIQ, promoting loading of the translesion polymerase domain. We speculate that removal of lagging strands at stalled forks by HeI308 promotes the formation of initiation zones, priming restart of lagging strand synthesis.