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Structure of the DNA repair helicase Hel308 reveals DNA binding and autoinhibitory domains

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Author(s)

J.D. Richards, K.A. Johnson, H. Liu, A-M. McRobbie, S. McMahon, M. Oke, L. Carter, James Henderson Naismith, Malcolm Frederick White

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Abstract

Hel308 is a superfamily 2 helicase conserved in eukaryotes and archaea. It is thought to function in the early stages of recombination following replication fork arrest and has a specificity for removal of the lagging strand in model replication forks. A homologous 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 structure 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 helicase 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.

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Original languageEnglish
Pages (from-to)5118-5126
Number of pages9
JournalJournal of Biological Chemistry
Volume283
Issue number8
DOIs
Publication statusPublished - 22 Feb 2008

    Research areas

  • STALLED REPLICATION FORKS, SINGLE-STRANDED-DNA, SULFOLOBUS-SOLFATARICUS, FLUORESCENCE POLARIZATION, ESCHERICHIA-COLI, PROTEIN, POLYMERASE, OLIGONUCLEOTIDES, ENDONUCLEASE, DISPLACEMENT

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