The structure of the XPF-ssDNA complex underscores the distinct roles of the XPF and ERCC1 helix- hairpin-helix domains in ss/ds DNA recognition

Devashish Das, Gert Folkers, Marc van Dijk, Nicolaas G.J. Jaspers, Jan H.J. Hoeijmakers, Robert Kaptein, Rolf Boelens

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

Human XPF/ERCC1 is a structure-specific DNA endonuclease that nicks the damaged DNA strand at the 5' end during nucleotide excision repair. We determined the structure of the complex of the C-terminal domain of XPF with 10 nt ssDNA. A positively charged region within the second helix of the first HhH motif contacts the ssDNA phosphate backbone. One guanine base is flipped out of register and positioned in a pocket contacting residues from both HhH motifs of XPF. Comparison to other HhH-containing proteins indicates a one-residue deletion in the second HhH motif of XPF that has altered the hairpin conformation, thereby permitting ssDNA interactions. Previous nuclear magnetic resonance studies showed that ERCC1 in the XPF-ERCC1 heterodimer can bind dsDNA. Combining the two observations gives a model that underscores the asymmetry of the human XPF/ERCC1 heterodimer in binding at an ss/ds DNA junction.

Original languageEnglish
Pages (from-to)667-75
Number of pages9
JournalStructure
Volume20
Issue number4
DOIs
Publication statusPublished - 4 Apr 2012

Keywords

  • Amino Acid Motifs
  • Binding Sites
  • DNA
  • DNA Repair
  • DNA, Single-Stranded
  • DNA-Binding Proteins
  • Endonucleases
  • Guanine
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Mutation
  • Protein Binding
  • Protein Multimerization
  • Protein Structure, Secondary
  • Recombinant Proteins
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
  • Static Electricity
  • Journal Article
  • Research Support, Non-U.S. Gov't

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