Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)

Rivera-Calzada, A., Maman, J. P., Spagnolo, L. , Pearl, L. H. and Llorca, O. (2005) Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure, 13(2), pp. 243-255. (doi: 10.1016/j.str.2004.12.006) (PMID:15698568)

Abstract

DNA-PKcs is a large PI3-kinase-related protein kinase (PIKK) that plays a central role in DNA double-strand break (DSB) repair via nonhomologous end joining. Using cryo-electron microscopy we have now generated a ∼13 Å three-dimensional map of DNA-PKcs, revealing the overall architecture and topology of the 4128 residue polypeptide chain and allowing location of domains. The highly conserved C-terminal PIKK catalytic domain forms a central structure from which FAT and FATC domains protrude. Conformational changes observed in these domains on DNA binding suggest that they transduce DNA-induced conformational changes to the catalytic core and regulate kinase activity. The N-terminal segments form long curved tubular-shaped domains based on helical repeats to create interacting surfaces required for macromolecular assembly. Comparison of DNA-PKcs with another PIKK DNA repair factor, ATM, defines a common architecture for this important protein family.

• Item Type: Articles
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Spagnolo, Professor Laura
• Authors: Rivera-Calzada, A., Maman, J. P., Spagnolo, L., Pearl, L. H., and Llorca, O.
• College/School: College of Medical Veterinary and Life Sciences > School of Molecular Biosciences
• Journal Name: Structure
• Publisher: Elsevier (Cell Press)
• ISSN: 0969-2126
• ISSN (Online): 1878-4186