Solution structure of the single-strand break repair protein XRCC1 N-terminal domain

Nat Struct Biol. 1999 Sep;6(9):884-93. doi: 10.1038/12347.

Abstract

XRCC1 functions in the repair of single-strand DNA breaks in mammalian cells and forms a repair complex with beta-Pol, ligase III and PARP. Here we describe the NMR solution structure of the XRCC1 N-terminal domain (XRCC1 NTD). The structural core is a beta-sandwich with beta-strands connected by loops, three helices and two short two-stranded beta-sheets at each connection side. We show, for the first time, that the XRCC1 NTD specifically binds single-strand break DNA (gapped and nicked). We also show that the XRCC1 NTD binds a gapped DNA-beta-Pol complex. The DNA binding and beta-Pol binding surfaces were mapped by NMR and found to be well suited for interaction with single-strand gap DNA containing a 90 degrees bend, and for simultaneously making contacts with the palm-thumb of beta-Pol in a ternary complex. The findings suggest a mechanism for preferential binding of the XRCC1 NTD to flexible single-strand break DNA.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • DNA / genetics
  • DNA / metabolism*
  • DNA Damage / genetics*
  • DNA Polymerase beta / metabolism*
  • DNA Repair* / genetics
  • DNA-Binding Proteins / chemistry*
  • DNA-Binding Proteins / metabolism
  • Evolution, Molecular
  • Glutamic Acid / genetics
  • Glutamic Acid / metabolism
  • Humans
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Magnetic Resonance, Biomolecular*
  • Pliability
  • Protein Binding
  • Protein Structure, Secondary
  • Sequence Alignment
  • Solutions
  • Thermodynamics
  • X-ray Repair Cross Complementing Protein 1

Substances

  • DNA-Binding Proteins
  • Solutions
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Glutamic Acid
  • DNA
  • DNA Polymerase beta

Associated data

  • PDB/1XNA
  • PDB/1XNT