anti-Phospho-DNA-PKcs (Ser2056) (human), Rabbit Monoclonal (RM500)

DNA-dependent protein kinase (DNA-PK) is an important factor in the repair of double-stranded breaks in DNA. Cells lacking DNA-PK or in which DNA-PK is inhibited fail to show proper nonhomologous end-joining (NHEJ). DNA-PK is composed of two DNA-binding subunits (Ku70 and Ku86) and one 450 kDa catalytic subunit (DNA-PKcs). It is thought that a heterodimer of Ku70 and Ku86 binds to double-stranded DNA broken ends before DNA-PKcs binds and is activated. Activated DNA-PKcs is a serine/threonine kinase that has been shown to phosphorylate a number of proteins in vitro, including p53, transcription factors, RNA polymerase, and Ku70/Ku86. DNA-PKcs autophosphorylation at multiple sites, including Thr2609 and Ser2056, results in an inactivation of DNA-PK kinase activity and NHEJ ability and may play a role in disassembly of the DNA repair machinery. Autophosphorylation at Thr2609 has also been shown to be required for DNA-PK-mediated double-strand break repair, and phosphorylated DNA-PK co-localizes with H2A.X and 53BP1 at sites of DNA damage. Phosphorylation at Ser2056 occurs in response to double-stranded DNA breaks and ATM activation. Higher expression of DNA-PK has been determined in several cancer tissues making it an interesting biomarker.