HELQ & Hel308: ancient enzymes of DNA repair and recombination.

We highlight the multifunctionality of the Hel308 and HELQ Ski2-like 'helicases' as they toggle between DNA annealing and DNA translocation across multiple DNA repair pathways. Defects in Hel308/HELQ cause genetic instability, including dysregulated homologous recombination. New data reveal how Hel308 and HELQ switch between DNA translocation and annealing, a mechanism that may restrain recombination to short tracts by curbing extensive DNA synthesis. We describe a PWI-like innovation in HELQ that evolved in bilaterian animals-absent from other animals and archaea-which we propose is an ATR-targeted phosphoregulatory module, coordinating protein interactions and, through those, DNA repair-recombination reactions. The overall picture is of Hel308 and HELQ as ancient DNA annealing enzymes, aided by short bursts of ATP-powered DNA translocation, kept in balance by molecular switches and the additional regulatory surfaces that arose in some animals.