Evidence for a remodelling of DNA-PK upon autophosphorylation from electron microscopy studies

Nucleic Acids Research

Volumn 39, Issue 13, 2011, Pages 5757-5767

  Morris, Edward P ^a   Rivera Calzada, Angel ^b,d   Da Fonseca, Paula C A ^a   Llorca, Oscar ^b   Pearl, Laurence H ^a,e   Spagnolo, Laura ^a,c  

^a INSTITUTE OF CANCER RESEARCH   (United Kingdom)

^b UNIVERSIDAD COMPLUTENSE DE MADRID   (Spain)

^c UNIVERSITY OF EDINBURGH   (United Kingdom)

^d UNIVERSITY OF LONDON   (United Kingdom)

^e UNIVERSITY OF SUSSEX   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

DNA DEPENDENT PROTEIN KINASE; KU ANTIGEN;

ARTICLE; AUTOPHOSPHORYLATION; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; DNA REPAIR; DOUBLE STRANDED DNA BREAK; ELECTRON MICROSCOPY; ENZYME ANALYSIS; ENZYME MECHANISM; ENZYME POLYMORPHISM; ENZYME STRUCTURE; HUMAN; HUMAN CELL; IMAGE ANALYSIS; PRIORITY JOURNAL; PROTEIN DNA INTERACTION; PROTEIN SECRETION; SEQUENCE ALIGNMENT; STRUCTURE ANALYSIS;

DIMERIZATION; DNA; DNA REPAIR; DNA-ACTIVATED PROTEIN KINASE; HELA CELLS; HUMANS; IMAGE PROCESSING, COMPUTER-ASSISTED; MICROSCOPY, ELECTRON; PHOSPHORYLATION;

EUKARYOTA;

EID: 80052199786     PISSN: 03051048     EISSN: 13624962     Source Type: Journal    
DOI: 10.1093/nar/gkr146     Document Type: Article

References (38)

1. van Gent, D.C., Hoeijmakers, J.H. and Kanaar, R. (2001) Chromosomal stability and the DNA double-stranded break connection. Nat. Rev. Genet., 2, 196.
2. West, S.C. (2003) Molecular views of recombination proteins and their control. Nat. Rev. Mol. Cell Biol., 4, 435.
3. Lieber, M.R. (2010) NHEJ and its backup pathways in chromosomal translocations, Nat. Struct. Mol. Biol., 17, 393.
4. Gottlieb, T.M. and Jackson, S.P. (1993) The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell, 72, 131.
5. Hartley, K.O., Gell, D., Smith, G.C., Zhang, H., Divecha, N., Connelly, M.A., Admon, A., Lees-Miller, S.P., Anderson, C.W. and Jackson, S.P. (1995) DNA-dependent protein kinase catalytic subunit: a relative of phosphatidylinositol 3-kinase and the ataxia telangiectasia gene product. Cell, 82, 849.
6. Abraham, R.T. (2004) PI 3-kinase related kinases: 'big' players in stress-induced signaling pathways. DNA Repair, 3, 883.
7. Downs, J.A. and Jackson, S.P. (2004) A means to a DNA end: the many roles of Ku. Nat. Rev. Mol. Cell Biol., 5, 367.
8. Walker, J.R., Corpina, R.A. and Goldberg, J. (2001) Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature, 412, 607.
9. Spagnolo, L., Rivera-Calzada, A., Pearl, L.H. and Llorca, O. (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.
10. Merkle, D., Douglas, P., Moorhead, G.B., Leonenko, Z., Yu, Y., Cramb, D., Bazett-Jones, D.P. and Lees-Miller, S.P. (2002) The DNA-dependent protein kinase interacts with DNA to form a protein-DNA complex that is disrupted by phosphorylation. Biochemistry, 41, 12706.
11. Douglas, P., Sapkota, G.P., Morrice, N., Yu, Y., Goodarzi, A.A., Merkle, D., Meek, K., Alessi, D.R. and Lees-Miller, S.P. (2002) Identification of in vitro and in vivo phosphorylation sites in the catalytic subunit of the DNA-dependent protein kinase. Biochem. J., 368, 243.
12. Block, W.D., Yu, Y., Merkle, D., Gifford, J.L., Ding, Q., Meek, K. and Lees-Miller, S.P. (2004) Autophosphorylation-dependent remodeling of the DNA-dependent protein kinase catalytic subunit regulates ligation of DNA ends. Nucleic Acids Res., 32, 4351.
13. Chan, D.W., Chen, B.P., Prithivirajsingh, S., Kurimasa, A., Story, M.D., Qin, J. and Chen, D.J. (2002) Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev., 16, 2333.
14. Chan, D.W. and Lees-Miller, S.P. (1996) The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J. Biol. Chem., 271, 8936.
15. Cui, X., Yu, Y., Gupta, S., Cho, Y.M., Lees-Miller, S.P. and Meek, K. (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.
16. Ding, Q., Reddy, Y.V., Wang, W., Woods, T., Douglas, P., Ramsden, D.A., Lees-Miller, S.P. and Meek, K. (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.
17. Goodarzi, A.A., Yu, Y., Riballo, E., Douglas, P., Walker, S.A., Ye, R., Harer, C., Marchetti, C., Morrice, N., Jeggo, P.A. et al. (2006) DNA-PK autophosphorylation facilitates Artemis endonuclease activity. EMBO J., 25, 3880.
18. Lou, Z., Chen, B.P., Asaithamby, A., Minter-Dykhouse, K., Chen, D.J. and Chen, J. (2004) MDC1 regulates DNA-PK autophosphorylation in response to DNA damage. J. Biol. Chem., 279, 46359.
19. Meek, K., Douglas, P., Cui, X., Ding, Q. and Lees-Miller, S.P. (2007) trans Autophosphorylation at DNA-dependent protein kinase's two major autophosphorylation site clusters facilitates end processing but not end joining. Mol. Cell. Biol., 27, 3881.
20. Reddy, Y.V., Ding, Q., Lees-Miller, S.P., Meek, K. and Ramsden, D.A. (2004) Non-homologous end joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends. J. Biol. Chem., 279, 39408.
21. Uematsu, N., Weterings, E., Yano, K., Morotomi-Yano, K., Jakob, B., Taucher-Scholz, G., Mari, P.O., van Gent, D.C., Chen, B.P. and Chen, D.J. (2007) Autophosphorylation of DNA-PKCS regulates its dynamics at DNA double-strand breaks. J. Cell. Biol., 177, 219.
22. Douglas, P., Cui, X., Block, W.D., Yu, Y., Gupta, S., Ding, Q., Ye, R., Morrice, N., Lees-Miller, S.P. and Meek, K. (2007) The DNA-dependent protein kinase catalytic subunit is phosphorylated in vivo on threonine 3950, a highly conserved amino acid in the protein kinase domain. Mol. Cell. Biol., 27, 1581.
23. Hammel, M., Yu, Y., Mahaney, B.L., Cai, B., Ye, R., Phipps, B.M., Rambo, R.P., Hura, G.L., Pelikan, M., So, S. et al. (2010) Ku and DNA-dependent protein kinase dynamic conformations and assembly regulate DNA binding and the initial non-homologous end joining complex. J. Biol. Chem., 285, 1414.
24. Leuther, K.K., Hammarsten, O., Kornberg, R.D. and Chu, G. (1999) Structure of DNA-dependent protein kinase: implications for its regulation by DNA. EMBO J., 18, 1114.
25. Chiu, C.Y., Cary, R.B., Chen, D.J., Peterson, S.R. and Stewart, P.L. (1998) Cryo-EM imaging of the catalytic subunit of the DNA-dependent protein kinase. J. Mol. Biol., 284, 1075.
26. Boskovic, J., Rivera-Calzada, A., Maman, J.D., Chacon, P., Willison, K.R., Pearl, L.H. and Llorca, O. (2003) Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J., 22, 5875.
27. Rivera-Calzada, A., Maman, J.D., 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, 243.
28. Williams, D.R., Lee, K.J., Shi, J., Chen, D.J. and Stewart, P.L. (2008) Cryo-EM structure of the DNA-dependent protein kinase catalytic subunit at subnanometer resolution reveals alpha helices and insight into DNA binding. Structure, 16, 468.
29. Sibanda, B.L., Chirgadze, D.Y. and Blundell, T.L. (2010) Crystal structure of DNA-PKcs reveals a large open-ring cradle comprised of HEAT repeats. Nature, 463, 118.
30. Llorca, O. and Pearl, L.H. (2004) Electron microscopy studies on DNA recognition by DNA-PK. Micron, 35, 625.
31. Rivera-Calzada, A., Spagnolo, L., Pearl, L.H. and Llorca, O. (2007) Structural model of full-length human Ku70-Ku80 heterodimer and its recognition of DNA and DNA-PKcs. EMBO Rep., 8, 56.
32. Dobbs, T.A., Tainer, J.A. and Lees-Miller, S.P. (2010) A structural model for regulation of NHEJ by DNA-PKcs autophosphorylation. DNA Repair, 9, 1307.
33. Ludtke, S.J., Baldwin, P.R. and Chiu, W. (1999) EMAN: semiautomated software for high-resolution single-particle reconstructions. J. Struct. Biol., 128, 82.
34. van Heel, M., Harauz, G., Orlova, E.V., Schmidt, R. and Schatz, M. (1996) A new generation of the IMAGIC image processing system. J. Struc. Biol., 116, 17.
35. Frank, J. (2006) Three-Dimensional Electron Microscopy of Macromolecular Assemblies: Visualization of Biological Molecules in their Native State. Oxford University Press, New York.
36. White, H.E., Saibil, H.R., Ignatiou, A. and Orlova, E.V. (2004) Recognition and separation of single particles with size variation by statistical analysis of their images. J. Mol. Biol., 336, 453.
37. Hanakahi, L.A. (2007) 2-Step purification of the Ku DNA repair protein expressed in Escherichia coli. Protein Expr. Purif., 52, 139.
38. Klaholz, B.P., Myasnikov, A.G. and Van Heel, M. (2004) Visualization of release factor 3 on the ribosome during termination of protein synthesis. Nature, 427, 862.