Structure of the DNA Repair Helicase Hel308 Reveals DNA Binding and Autoinhibitory Domains*

Jodi D. Richards1, Kenneth A. Johnson1, Huanting Liu, Anne-Marie McRobbie, Stephen McMahon, Muse Oke, Lester Carter, James H. Naismith2, and Malcolm F. White3

Research output: Contribution to journalArticlepeer-review

65 Citations (Scopus)

Abstract

Hel308 is a superfamily 2 helicase conserved in eukaryotes and archaea. It is thought to function in the early stages of recombina- tion following replication fork arrest and has a specificity for removal of the lagging strand in model replication forks. A homol- ogous helicase constitutes the N-terminal domain of human DNA polymerase Q. The Drosophila homologue mus301 is implicated in double strand break repair and meiotic recombination. We have solved the high resolution crystal structure of Hel308 from the cre- narchaeon Sulfolobus solfataricus, revealing a five-domain struc- ture with a central pore lined with essential DNA binding residues. The fifth domain is shown to act as an autoinhibitory domain or molecular brake, clamping the single-stranded DNA extruded through the central pore of the helicase structure to limit the heli- case activity of the enzyme. This provides an elegant mechanism to tune the processivity of the enzyme to its functional role. Hel308 can displace streptavidin from a biotinylated DNA molecule, and this activity is only partially inhibited when the DNA is pre-bound with abundant DNA-binding proteins RPA or Alba1, whereas pre- binding with the recombinase RadA has no effect on activity. These data suggest that one function of the enzyme may be in the removal of bound proteins at stalled replication forks and recombination intermediates.
Original languageEnglish
Pages (from-to)5118-5126
JournalJournal of Biological Chemistry
Volume283
Issue number8
Publication statusPublished - 22 Feb 2008

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