Crystal structure of a xeroderma pigmentosum group F endonuclease with and without DNA suggests a model for recognition of branched DNA substrates

M Newman, J Murray-Rust, J Lally, J Rudolf, A Fadden, P Knowles, Malcolm Frederick White, NQ McDonald

Research output: Contribution to journalArticlepeer-review

100 Citations (Scopus)

Abstract

The XPF/Mus81 structure-specific endonucleases cleave double-stranded DNA ( dsDNA) within asymmetric branched DNA substrates and play an essential role in nucleotide excision repair, recombination and genome integrity. We report the structure of an archaeal XPF homodimer alone and bound to dsDNA. Superposition of these structures reveals a large domain movement upon binding DNA, indicating how the (HhH)(2) domain and the nuclease domain are coupled to allow the recognition of double-stranded/single-stranded DNA junctions. We identify two nonequivalent DNA-binding sites and propose a model in which XPF distorts the 30 flap substrate in order to engage both binding sites and promote strand cleavage. The model rationalises published biochemical data and implies a novel role for the ERCC1 subunit of eukaryotic XPF complexes.

Original languageEnglish
Pages (from-to)895-905
Number of pages11
JournalEMBO Journal
Volume24
DOIs
Publication statusPublished - 9 Mar 2005

Keywords

  • archaea
  • DNA repair
  • endonuclease
  • HhH domain
  • XPF
  • NUCLEOTIDE EXCISION-REPAIR
  • XERODERMA-PIGMENTOSUM
  • HOLLIDAY JUNCTIONS
  • CRYSTAL-STRUCTURE
  • AEROPYRUM-PERNIX
  • PROTEINS
  • BINDING
  • ERCC1
  • MUS81-EME1
  • NUCLEASE

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