trans Autophosphorylation at DNA-Dependent Protein Kinase's Two Major Autophosphorylation Site Clusters Facilitates End Processing but Not End Joining

REFERENCES

• Block, W., Y. Yu, D. Merkle, J. Gifford, Q. Ding, K. Meek, and S. P. Lees-Miller. 2004. Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs) regulates ligation of DNA ends. Nucleic Acids Res. 32:4351–4357.
   PubMed Web of Science ®Google Scholar
• Boskovic, J., A. Rivera-Calzada, J. D. Maman, P. Chacon, K. R. Willison, L. H. Pearl, and O. Llorca. 2003. Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J. 22:5875–5882.
   PubMedGoogle Scholar
• Chan, D. W., B. P. Chen, S. Prithivirajsingh, A. Kurimasa, M. D. Story, J. Qin, and D. J. Chen. 2002. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev. 16:2333–2338.
   PubMed Web of Science ®Google Scholar
• Chan, D. W., and S. P. Lees-Miller. 1996. The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J. Biol. Chem. 271:8936–8941.
   PubMed Web of Science ®Google Scholar
• Chen, B. P., N. Uematsu, J. Kobayashi, Y. Lerenthal, A. Krempler, H. Yajima, M. Lobrich, Y. Shiloh, and D. J. Chen. 2006. Ataxia telangiectasia mutated (ATM) is essential for DNA-PKcs phosphorylations at the Thr-2609 cluster upon DNA double strand break. J. Biol. Chem. 282:6582–6587.
   PubMedGoogle Scholar
• Chen, B. P., D. W. Chan, J. Kobayashi, S. Burma, A. Asaithamby, K. Morotomi-Yano, E. Botvinick, J. Qin, and D. J. Chen. 2005. Cell cycle dependence of DNA-dependent protein kinase phosphorylation in response to DNA double strand breaks. J. Biol. Chem. 280:14709–14715.
   PubMed Web of Science ®Google Scholar
• Convery, E., E. K. Shin, Q. Ding, W. Wang, P. Douglas, L. S. Davis, J. A. Nickoloff, S. P. Lees-Miller, and K. Meek. 2005. Inhibition of homologous recombination by variants of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs). Proc. Natl. Acad. Sci. USA 102:1345–1350.
   PubMedGoogle Scholar
• Cui, X., T. Yu, S. Gupta, Y. M. Cho, S. P. Lees-Miller, and K. Meek. 2005. Autophosphorylation of DNA-dependent protein kinase regulates DNA end processing and may also alter double-strand break repair pathway choice. Mol. Cell. Biol. 25:10842–10852.
   PubMed Web of Science ®Google Scholar
• Ding, Q., Y. V. Reddy, W. Wang, T. Woods, P. Douglas, D. A. Ramsden, S. P. Lees-Miller, and K. Meek. 2003. Autophosphorylation of the catalytic subunit of the DNA-dependent protein kinase is required for efficient end processing during DNA double-strand break repair. Mol. Cell. Biol. 23:5836–5848.
   PubMed Web of Science ®Google Scholar
• Douglas, P., W. D. Block, X. Cui, Y. Yu, Q. Ding, R. Ye, S. Gupta, N. Morrice, S. P. Lees-Miller, and K. Meek. 2007. The DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is phosphorylated in vivo on threonine 3950, a highly conserved amino acid in the protein kinase domain. Mol. Cell. Biol. 27:1581–1591.
   PubMed Web of Science ®Google Scholar
• Douglas, P., G. B. Moorhead, R. Ye, and S. P. Lees-Miller. 2001. Protein phosphatases regulate DNA-dependent protein kinase activity. J. Biol. Chem. 276:18992–18998.
   PubMedGoogle Scholar
• Douglas, P., G. P. Sapkota, N. Morrice, Y. Yu, A. A. Goodarzi, D. Merkle, K. Meek, D. R. Alessi, and S. P. Lees-Miller. 2002. Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase. Biochem. J. 368:243–251.
   PubMed Web of Science ®Google Scholar
• Gupta, S., and K. Meek. 2005. The leucine rich region of DNA-PKcs contributes to its innate DNA affinity. Nucleic Acids Res. 33:6972–6981.
   PubMedGoogle Scholar
• Kienker, L. J., E. K. Shin, and K. Meek. 2000. Both V(D)J recombination and radioresistance require DNA-PK kinase activity, though minimal levels suffice for V(D)J recombination. Nucleic Acids Res. 28:2752–2761.
   PubMedGoogle Scholar
• Lees-Miller, S. P., and K. Meek. 2003. Repair of DNA double strand breaks by non-homologous end joining. Biochemie 85:1161–1173.
   PubMed Web of Science ®Google Scholar
• Meek, K., S. Gupta, D. A. Ramsden, and S. P. Lees-Miller. 2004. DNA-PK: activity director at the end. Immunol. Rev. 200:132–141.
   PubMed Web of Science ®Google Scholar
• Merkle, D., P. Douglas, G. B. Moorhead, Z. Leonenko, Y. Yu, D. Cramb, D. P. Bazett-Jones, and S. P. Lees-Miller. 2002. The DNA dependent protein kinase interacts with DNA to form a protein DNA complex that is disrupted by phosphorylation. Biochemistry 41:12706–12714.
   PubMed Web of Science ®Google Scholar
• Reddy, V., Q. Ding, S. P. Lees-Miller, K. Meek, and D. A. Ramsden. 2004. Nonhomologous end-joining requires the DNA-PK complex to undergo remodeling at DNA ends. J. Biol. Chem. 279:39408–39413.
   PubMedGoogle Scholar
• Rivera-Calzada, A., J. D. Maman, L. Spagnolo, L. H. Pearl, and O. Llorca. 2005. Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure 13:243–255.
   PubMed Web of Science ®Google Scholar
• Soubeyrand, S., L. Pope, B. Pakuts, and R. J. Hache. 2003. Threonines 2638/2647 in DNA-PK are essential for cellular resistance to ionizing radiation. Cancer Res. 63:1198–1201.
   PubMed Web of Science ®Google Scholar
• Spagnolo, L., A. Rivera-Calzada, L. H. Pearl, and O. Llorca. 2006. Three-dimensional structure of the human DNA-PKcs/Ku70/Ku80 complex assembled on DNA and its implications for DNA DSB repair. Mol. Cell 22:511–519.
   PubMed Web of Science ®Google Scholar
• Wechsler, T., B. P. Chen, R. Harper, K. Morotomi-Yano, B. C. Huang, K. Meek, J. E. Cleaver, D. J. Chen, and M. Wabl. 2004. DNA-PKcs function regulated specifically by protein phosphatase 5. Proc. Natl. Acad. Sci. USA 101:1247–1252.
   PubMed Web of Science ®Google Scholar
• Woods, T., W. Wang, E. Convery, A. Errami, M. Z. Zdzienicka, and K. Meek. 2002. A single amino acid substitution in DNA-PKcs explains the novel phenotype of the CHO mutant, XR-C2. Nucleic Acids Res. 30:5120–5128.
   PubMedGoogle Scholar
• Yajima, H., K. J. Lee, and B. P. Chen. 2006. ATR-dependent DNA-PKcs phosphorylation in response to UV-induced replication stress. Mol. Cell. Biol. 26:7520–7528.
   PubMed Web of Science ®Google Scholar