InterPro domain: IPR001357

The breast cancer susceptibility gene contains at its C terminus two copies of a conserved domain that was named BRCT for BRCA1 C terminus. This domain of about 95 amino acids is found in a large variety of proteins involved in DNA repair, recombination and cell cycle control [ 1 , 2 , 3 ]. The BRCT domain is not limited to the C-terminal of protein sequences and can be found in multiple copies or in a single copy as in RAP1 and TdT. BRCT domains are often found as tandem-repeat pairs [ 4 ]. Some data [ 5 ] indicate that the BRCT domain functions as a protein-protein interaction module.

The structure of the first of the two C-terminal BRCT domains of the human DNA repair protein XRCC1 has been determined by X-ray crystallography [ 6 ].

Structures of the BRCA1 BRCT domains revealed a basis for a widely utilised head-to-tail BRCT-BRCT oligomerization mode [ 6 ]. This conserved tandem BRCT architecture facilitates formation of the canonical BRCT phospho-peptide interaction cleft at a groove between the BRCT domains. BRCT domains disrupt peptide binding by directly occluding this peptide binding groove, or by disrupting key conserved BRCT core folding determinants [ 7 ].

1. BRCA1 protein products ... Functional motifs... Nat. Genet. 13, 266-8
2. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. FASEB J. 11, 68-76
3. From BRCA1 to RAP1: a widespread BRCT module closely associated with DNA repair. FEBS Lett. 400, 25-30
4. Interactions between BRCT repeats and phosphoproteins: tangled up in two. Trends Biochem. Sci. 29, 579-85
5. Structure of an XRCC1 BRCT domain: a new protein-protein interaction module. EMBO J. 17, 6404-11
6. Crystal structure of the BRCT repeat region from the breast cancer-associated protein BRCA1. Nat. Struct. Biol. 8, 838-42
7. Structural basis of phosphopeptide recognition by the BRCT domain of BRCA1. Nat. Struct. Mol. Biol. 11, 519-25