Solution structure and DNA binding of the zinc-finger domain from DNA ligase IIIalpha

J Mol Biol. 2004 Aug 13;341(3):723-38. doi: 10.1016/j.jmb.2004.06.035.

Abstract

DNA ligase IIIalpha carries out the final ligation step in the base excision repair (BER) and single strand break repair (SSBR) mechanisms of DNA repair. The enzyme recognises single-strand nicks and other damage features in double-stranded DNA, both through the catalytic domain and an N-terminal domain containing a single zinc finger. The latter is homologous to other zinc fingers that recognise damaged DNA, two in the N terminus of poly(adenosine-ribose)polymerase and three in the N terminus of the Arabidopsis thaliana nick-sensing DNA 3'-phosphoesterase. Here, we present the solution structure of the zinc-finger domain of human DNA ligase IIIalpha, the first structure of a finger from this group. It is related to that of the erythroid transcription factor GATA-1, but has an additional N-terminal beta-strand and C-terminal alpha-helix. Chemical shift mapping using a DNA ligand containing a single-stranded break showed that the DNA-binding surface of the DNA-ligase IIIalpha zinc finger is substantially different from that of GATA-1, consistent with the fact that the two proteins recognise very different features in the DNA. Likely implications for DNA binding are discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Arabidopsis / enzymology
  • Base Sequence
  • DNA / chemistry*
  • DNA Ligase ATP
  • DNA Ligases / chemistry*
  • DNA Repair
  • DNA-Binding Proteins / metabolism
  • Databases as Topic
  • Erythroid-Specific DNA-Binding Factors
  • Escherichia coli / metabolism
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Sequence Data
  • Nucleic Acid Conformation
  • Poly-ADP-Ribose Binding Proteins
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Homology, Amino Acid
  • Software
  • Transcription Factors / metabolism
  • Xenopus Proteins
  • Zinc Fingers

Substances

  • DNA-Binding Proteins
  • Erythroid-Specific DNA-Binding Factors
  • Ligands
  • Poly-ADP-Ribose Binding Proteins
  • Transcription Factors
  • Xenopus Proteins
  • DNA
  • DNA Ligases
  • DNA Ligase ATP
  • DNA ligase III alpha protein, Xenopus

Associated data

  • PDB/1UW0