Abstract

BRCT domains were first identified in and named after the breast cancer susceptibility protein BRCA1 (Zhang et al.,1998). They have alpha/beta structures that occur singly or as multiple repeats. BRCT domains are 80-100 amino acid in length and function as phosphopeptide ligands (Clapperton et al.,2004). They are found in nuclear proteins that are typically associated with cell cycle checkpoint functions responsive to DNA damage (Glover et al.,2004). An unusual feature of paired BRCT motifs is that the phosphopeptides bind across the domain-domain interface (Clapperton et al.,2004). Available data when this entry was prepared suggest that BRCTs may bind exclusively to phosphoserine peptides. By contrast FHA domains, which are often found in a similar functional context, recognise phosphothreonine peptides (LIG_FHA_1). Many of the BRCT ligands are likely to be at pSQ motifs phosphorylated by the checkpoint kinases, ATM, ATR, DNA-PK (Glover et al.,2004). BRCA1-binding motifs are S..F.K (high affinity) or S..F (lower affinity) (Clapperton et al.,2004). Metazoan MDC1 binds histone H2AX C-terminal motifs S..Y$ (Lee et al.,2005) [which may be S..F$ in plants and S..L$ in fungi, but experimental evidence has been lacking]. A poorly characterised motif binding the TopBP1 BRCT may match the pattern S.II but more data is needed (Liu et al.,2003). Since consensus motifs have so far been defined for just a few BRCT domains, the range of different binding motif patterns could be quite large.