LIG4 BRCT domains (human, recombinant)

DNA Ligase 4 (LIG4) is a large protein belonging to the ATP-dependent DNA ligase family.¹ LIG4 contains two BRCA1 C-terminal (BRCT) domains. 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.^2,3 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 RAD9.⁴ 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.^5,4 Thus, BRCT domain-containing proteins likely participate in the cellular response to DNA damage. LIG4 forms a complex with the DNA repair protein Xrcc4 to play an essential role in DNA non-homologous end joining during DNA double-strand break repair and V(D)J recombination, which is the rearrangement of immunoglobulin and T-cell receptor genes.^6,7,8 Cells lacking either of these proteins are hypersensitive to ionizing radiation. Mutations of the gene that encodes this protein results in an autosomal recessive disease called LIG4 syndrome, which is characterized by microcephaly, unusual facial features, growth retardation, developmental delay, skin anomalies, and is associated with pancytopenia (reduction of red blood cells, white blood cells, and platelets).^9,10 This protein product contains the tandem BRCT domain region of LIG4.

WARNING This product is not for human or veterinary use.

1. Wei, Y.F., Robins, P., Carter, K., et al. Molecular cloning and expression of human cDNAs encoding a novel DNA ligase IV and DNA ligase III, an enzyme active in DNA repair and recombination. Mol. Cell. Biol. 15(6), 3206-3216 (1995).

2. 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).

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. 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).

5. 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).

6. Critchlow, S.E., Bowater, R.P., and Jackson, S.P. Mammalian DNA double-strand break repair protein XRCC4 interacts with DNA ligase IV. Curr. Biol. 7(8), 588-598 (1997).

7. Sibanda, B.L., Critchlow, S.E., Begun, J., et al. Crystal structure of an Xrcc4-DNA ligase IV complex. Nat. Struct. Biol. 8(12), 1015-1019 (2001).

8. Grawunder, U., Zimmer, D., Fugmann, S., et al. DNA ligase IV is essential for V(D)J recombination and DNA double-strand break repair in human precursor lymphocytes. Mol. Cell 2(4), 477-484 (1998).

9. Chistiakov, D.A., Voronova, N.V., and Chistiakov, A.P. Ligase IV syndrome. Eur. J. Med. Genet. 52(6), 373-378 (2009).

10. O'Driscoll, M., Cerosaletti, K.M., Girard, P.M., et al. DNA ligase IV mutations identified in patients exhibiting developmental delay and immunodeficiency. Mol. Cell 8(6), 1175-1185 (2001).