Role of a BRCT domain in the interaction of DNA ligase III-alpha with the DNA repair protein XRCC1

Curr Biol. 1998 Jul 16;8(15):877-80. doi: 10.1016/s0960-9822(07)00350-8.


The BRCT domain (for BRCA1 carboxyl terminus) is a protein motif of unknown function, comprising approximately 100 amino acids in five conserved blocks denoted A-E. BRCT domains are present in the tumour suppressor protein BRCA1 [1-3], and the domain is found in over 40 other proteins, defining a superfamily that includes DNA ligase III-alpha and the essential human DNA repair protein XRCC1. DNA ligase III-alpha and XRCC1 interact via their carboxyl termini, close to or within regions that contain a BRCT domain [4]. To examine whether the primary role of the carboxy-terminal BRCT domain of XRCC1 (denoted BRCT II) is to mediate the interaction with DNA ligase III-alpha, we identified the regions of the domain that are required and sufficient for the interaction. An XRCC1 protein in which the conserved D-block tryptophan was disrupted by point mutation retained the ability to interact with DNA ligase III-alpha, so this tryptophan must mediate a different, although conserved, role. XRCC1 in which the weakly conserved C-block was mutated lost the ability to interact with DNA ligase III-alpha. Moreover, 20 amino acids spanning the C-block of BRCT II conferred full DNA ligase III-alpha binding activity upon an unrelated polypeptide. An XRCC1 protein in which this 20mer was deleted could not maintain normal levels of DNA ligase III-alpha in transfected rodent cells, a phenotype associated with defective repair [5]. In summary, these data demonstrate that a BRCT domain can mediate a biologically important protein-protein interaction, and support the existence of additional roles.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • BRCA1 Protein / genetics
  • BRCA1 Protein / metabolism*
  • CHO Cells
  • Cricetinae
  • DNA Ligase ATP
  • DNA Ligases / genetics
  • DNA Ligases / metabolism*
  • DNA Repair*
  • DNA-Binding Proteins / metabolism*
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Poly-ADP-Ribose Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • Xenopus Proteins


  • BRCA1 Protein
  • DNA-Binding Proteins
  • Poly-ADP-Ribose Binding Proteins
  • X-ray Repair Cross Complementing Protein 1
  • XRCC1 protein, human
  • Xenopus Proteins
  • DNA Ligases
  • DNA Ligase ATP
  • DNA ligase III alpha protein, Xenopus
  • LIG3 protein, human