BARD1 BRCT domains (human, recombinant)

BRCA1-associated RING domain protein 1 (BARD1) is a binding partner of the breast and ovarian tumor suppressor (BRCA1).^1,2 BARD1 binding to BRCA1 via the RING and BRCT domains regulates BRCA1 stability, cellular localization, and function.^2,3,4 Heterodimeric BRCA1/BARD1 enhances BRCA1 functions, including the maintenance of genomic stability by participating in DNA repair mechanisms.³ Further, BRCA1/BARD1 heterodimers have been shown to have ubiquitin ligase activity.⁵ BARD1 has also been shown to mediate p53-dependent, BRCA1-independent apoptosis.^6,7 BARD1 binding to the mRNA polyadenylation factor, cleavage stimulation factor-50, is involved in inhibiting mRNA processing and tumor suppression.^8,9 BARD1 contains two BRCA1 C-terminal (BRCT) domains.¹ BRCT domains are modular units of ~100 amino acids that fold independently and recognize linear phosphoserine or phosphothreonine regions to mediate protein-protein and protein-DNA interactions.^10,11 BRCT domains were initially recognized in the C-terminal region of the breast cancer protein BRCA1, as well as the p53 binding protein and the yeast cell cycle checkpoint protein RAD9.¹² BRCT domains often occur as tandem repeats at the C-terminal end of several proteins that are functionally diverse.¹¹ Most BRCT domain-containing proteins participate in DNA-damage checkpoint control or DNA-repair pathways, or both.^13,12 Thus, BRCT domain-containing proteins likely participate in the cellular response to DNA damage. This recombinant protein product contains the first and second BRCT domains of BARD1.

WARNING This product is not for human or veterinary use.

1. Wu, L.C., Wang, Z.W., Tsan, J.T., et al. Identification of a RING protein that can interact in vivo with the BRCA1 gene product. Nat. Genet. 14(4), 430-440 (1996).

2. Irminger-Finger, I., and Jefford, C.E. Is there more to BARD1 than BRCA1? Nat. Rev. Cancer 6(5), 382-391 (2006).

3. Simons, A.M., Horwitz, A.A., Starita, L.M., et al. BRCA1 DNA-binding activity is stimulated by BARD1. Cancer Res. 66(4), 2012-2018 (2006).

4. Baer, R., and Ludwig, T. The BRCA1/BARD1 heterodimer, a tumor suppressor complex with ubiquitin E₃ ligase activity. Curr. Opin. Genet. Dev. 12(1), 86-91 (2002).

5. Brzovic, P.S., Keeffe, J.R., Nishikawa, H., et al. Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex. Proc. Natl. Acad. Sci. USA 100(10), 5646-5651 (2003).

6. Feki, A., Jefford, C.E., Berardi, P., et al. BARD1 induces apoptosis by catalysing phosphorylation of p53 by DNA-damage response kinase. Oncogene 24(23), 3726-3736 (2005).

7. Irminger-Finger, I., Leung, W.C., Li, J., et al. Identification of BARD1 as mediator between proapoptotic stress and p53-dependent apoptosis. Mol. Cell 8(6), 1255-1266 (2001).

8. Irminger-Finger, I., and Leung, W.C. BRCA1-dependent and independent functions of BARD1. Int. J. Biochem. Cell Biol. 34(6), 582-587 (2014).

9. Kleiman, F.E., and Manley, J.L. Functional interaction of BRCA1-associated BARD1 with polyadenylation factor CstF-50. Science 285(5433), 1576-1579 (1999).

10. 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).

11. 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).

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

13. 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).