TP53BP1 BRCT domains (human, recombinant)

The BRCA1 C-terminal (BRCT) domain is a modular unit of ~100 amino acids that folds independently and recognizes linear phosphoserine or phosphothreonine regions to mediate protein-protein and protein-DNA interactions.¹ BRCT domains were initially recognized in the C-terminal region of the breast cancer protein BRCA1, as well as the p53 binding protein (53BP1; TP53BP1), and the yeast cell cycle checkpoint protein RAD9.² BRCT domains often occur as tandem repeats at the C-terminal end of several proteins that are functionally diverse.³ Most BRCT domain-containing proteins participate in DNA-damage checkpoint control or DNA-repair pathways, or both.^4,2 Thus, BRCT domain-containing proteins likely participate in the cellular response to DNA damage. The BRCT domains of TP53BP1 bind to the DNA binding domain region of the tumor suppressor protein p53. The residues of p53 involved in this binding are often mutated in cancer.^5,6,7 Binding of TP53BP1 to p53 occurs through the first BRCT domain and the inter-domain linker between the BRCT repeats. TP53BP1 binds to wild-type but not mutant p53 protein, which was believed to mediate p53 tumor suppressor function.⁶ More recently, recruitment to DNA double strand breaks has shown to be mediated by the TP53BP1 tudor domain region binding to dimethylated lysine on p53 and histone H4.^8,9 This product contains the BRCT domains of TP53BP1.

WARNING This product is not for human or veterinary use.

1. Manke, I.A., Lowery, D.M., Nguyen, A., et al. BRCT repeats as phosphopeptide-binding modules involved in protein targeting. Science 302(5645), 636-639 (2003).

2. Bork, P., Hofmann, K., Bucher, P., et al. A superfamily of conserved domains in DNA damage-responsive cell cycle checkpoint proteins. The FASEB Journal 11(1), 68-76 (1997).

3. Woods, N.T., Mesquita, R.D., Sweet, M., et al. Charting the landscape of tandem BRCT domain-mediated protein interactions. Sci. Signal. 5(242), rs6 (2012).

4. Callebaut, I., and Mornon, J.P. From BRCA1 to RAP1: A widespread BRCT module closely associated with DNA repair. FEBS Lett. 400(1), 25-30 (1997).

5. Derbyshire, D.J., Basu, B.P., Serpell, L.C., et al. Crystal structure of human 53BP1 BRCT domains bound to p53 tumour suppressor. EMBO J. 21(4), 3863-3872 (2002).

6. Iwabuchi, K., Bartel, P.L., Li, B., et al. Two cellular proteins that bind to wild-type but not mutant p53. Proc. Natl. Acad. Sci. USA 91(13), 6098-6102 (1994).

7. Joo, W.S., Jeffrey, P.D., Cantor, S.B., et al. Structure of the 53BP1 BRCT region bound to p53 and its comparison to the Brca1 BRCT structure. Genes Dev. 16(5), 583-593 (2002).

8. Kachirskaia, I., Shi, X., Yamaguchi, H., et al. Role for 53BP1 tudor domain recognition of p53 dimethylated at lysine 382 in DNA damage signaling. The Journal of Biological Chemisty 283(50), 34660-34666 (2008).

9. Zgheib, O., Pataky, K., Brugger, J., et al. An oligomerized 53BP1 tudor domain suffices for recognition of DNA double-strand breaks. Mol. Cell. Biol. 29(4), 1050-1058 (2009).