Nanomedicine: Nanotechnology, Biology and Medicine
Volume 2, Issue 2 , Pages 74-81 , June 2006

Modifying the function of DNA repair nanomachines for therapeutic benefit

Material in this article was originally presented at the First Annual Meeting of the American Academy of Nanomedicine, Baltimore, MD, August 15-16, 2005.

Received 2 February 2006 ,Accepted 7 April 2006.

References 

  1. Ward JF. Nature of lesions formed by ionizing radiation. In:  Nickoloff JA,  Hoekstra MF editor. DNA damage and repair. Vol. II. Totowa, NJ: Humana Press; 1998;p. 65–84
  2. Di Leonardo A, Linke SP, Clarkin K, Wahl GM. DNA damage triggers a prolonged p53-dependent G1 arrest and long-term induction of Cip1 in normal human fibroblasts. Genes Dev. 1994;8:2540–2551
  3. Metzger L, Iliakis G. Kinetics of DNA double-strand break repair throughout the cell cycle as assayed by pulsed field gel electrophoresis in CHO cells. Int J Radiat Biol. 1991;59:1325–1339
  4. Sonoda E, Takata M, Yamashita YM, Morrison C, Takeda S. Homologous DNA recombination in vertebrate cells. Proc Natl Acad Sci USA. 2001;98:8388–8394
  5. Featherstone C, Jackson SP. DNA double-strand break repair. Curr Biol. 1999;9:R759–R761
  6. Collis SJ, DeWeese TL, Jeggo PA, Parker AR. The life and death of DNA-PK. Oncogene. 2005;24:949–961
  7. Rogakou EP, Boon C, Redon C, Bonner WM. Megabase chromatin domains involved in DNA double-strand breaks in vivo. J Cell Biol. 1999;146:905–916
  8. Bassing CH, Alt FW. H2AX may function as an anchor to hold broken chromosomal DNA ends in close proximity. Cell Cycle. 2004;3:149–153
  9. Schultz LB, Chehab NH, Malikzay A, Halazonetis TD. p53 binding protein 1 (53BP1) is an early participant in the cellular response to DNA double-strand breaks. J Cell Biol. 2000;151:1381–1390
  10. Stewart GS, Wang B, Bignell CR, Taylor AM, Elledge SJ. MDC1 is a mediator of the mammalian DNA damage checkpoint. Nature. 2003;421:961–966
  11. Ward IM, Wu X, Chen J. Threonine 68 of Chk2 is phosphorylated at sites of DNA strand breaks. J Biol Chem. 2001;276:47755–47758
  12. Xu X, Stern DF. NFBD1/MDC1 regulates ionizing radiation-induced focus formation by DNA checkpoint signaling and repair factors. FASEB J. 2003;17:1842–1848
  13. Kao GD, McKenna WG, Guenther MG, Muschel RJ, Lazar MA, Yen TJ. Histone deacetylase 4 interacts with 53BP1 to mediate the DNA damage response. J Cell Biol. 2003;160:1017–1027
  14. Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, et al. Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome. Cell. 1998;93:467–476
  15. Carney JP, Maser RS, Olivares H, Davis EM, Le Beau M, Yates JR, et al. The hMre11/hRad50 protein complex and Nijmegen breakage syndrome: linkage of double-strand break repair to the cellular DNA damage response. Cell. 1998;93:477–486
  16. Yoo S, Kimzey A, Dynan WS. Photocross-linking of an oriented DNA repair complex. Ku bound at a single DNA end. J Biol Chem. 1999;274:20034–20039
  17. Yoo S, Dynan WS. Geometry of a complex formed by double strand break repair proteins at a single DNA end: recruitment of DNA-PKcs induces inward translocation of Ku protein. Nucleic Acids Res. 1999;27:4679–4686
  18. Mimori T, Hardin JA. Mechanism of interaction between Ku protein and DNA. J Biol Chem. 1986;261:10375–10379
  19. Dvir A, Peterson SR, Knuth MW, Lu H, Dynan WS. Ku autoantigen is the regulatory component of a template-associated protein kinase that phosphorylates RNA polymerase II. Proc Natl Acad Sci USA. 1992;89:11920–11924
  20. Gottlieb TM, Jackson SP. The DNA-dependent protein kinase: requirement for DNA ends and association with Ku antigen. Cell. 1993;72:131–142
  21. Walker JR, Corpina RA, Goldberg J. Structure of the Ku heterodimer bound to DNA and its implications for double-strand break repair. Nature. 2001;412:607–614
  22. Rivera-Calzada A, Maman JD, Spagnolo L, Pearl LH, Llorca O. Three-dimensional structure and regulation of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Structure (Camb). 2005;13:243–255
  23. Chan DW, Lees-Miller SP. The DNA-dependent protein kinase is inactivated by autophosphorylation of the catalytic subunit. J Biol Chem. 1996;271:8936–8941
  24. DeFazio LG, Stansel RM, Griffith JD, Chu G. Synapsis of DNA ends by DNA-dependent protein kinase. EMBO J. 2002;21:3192–3200
  25. Ding Q, Reddy YV, Wang W, Woods T, Douglas P, Ramsden DA, et al. 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. 2003;23:5836–5848
  26. Reddy YV, Ding Q, Lees-Miller SP, Meek K, Ramsden DA. Nonhomologous end-joining requires that the DNA-PK complex undergo an autophosphorylation-dependent rearrangement at DNA ends. J Biol Chem. 2004;279:39408–39413
  27. Lee KJ, Huang J, Takeda Y, Dynan WS. DNA ligase IV and XRCC4 form a stable mixed tetramer that functions synergistically with other repair factors in a cell-free end-joining system. J Biol Chem. 2000;275:34787–34796
  28. Sibanda BL, Critchlow SE, Begun J, Pei XY, Jackson SP, Blundell TL, et al. Crystal structure of an Xrcc4-DNA ligase IV complex. Nat Struct Biol. 2001;8:1015–1019
  29. Chan DW, Chen BP, Prithivirajsingh S, Kurimasa A, Story MD, Qin J, et al. Autophosphorylation of the DNA-dependent protein kinase catalytic subunit is required for rejoining of DNA double-strand breaks. Genes Dev. 2002;16:2333–2338
  30. Trodella L, D'Angelillo RM, Ramella S, Ciresa M, Massaccesi M. Dose fractionation and biological optimization in lung cancer. Rays. 2004;29:319–326
  31. Willner J, Baier K, Caragiani E, Tschammler A, Flentje M. Dose, volume, and tumor control prediction in primary radiotherapy of non-small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2002;52:382–389
  32. Sirzen F, Nilsson A, Zhivotovsky B, Lewensohn R. DNA-dependent protein kinase content and activity in lung carcinoma cell lines: correlation with intrinsic radiosensitivity. Eur J Cancer. 1999;35:111–116
  33. Bird RE, Hardman KD, Jacobson JW, Johnson S, Kaufman BM, Lee SM, et al. Single-chain antigen-binding proteins. Science. 1988;242:423–426
  34. Carter T, Vancurova I, Sun I, Lou W, DeLeon S. A DNA-activated protein kinase from HeLa cell nuclei. Mol Cell Biol. 1990;10:6460–6471
  35. Li S, Takeda Y, Wragg S, Barrett J, Phillips AC, Dynan WS. Modification of the ionizing radiation response in living cells by an scFv against the DNA-dependent protein kinase. Nucleic Acids Res. 2003;31:5848–5857
  36. Boskovic J, Rivera-Calzada A, Maman JD, Chacon P, Willison KR, Pearl LH, et al. Visualization of DNA-induced conformational changes in the DNA repair kinase DNA-PKcs. EMBO J. 2003;22:5875–5882
  37. Blint E, Phillips AC, Kozlov S, Stewart CL, Vousden KH. Induction of p57(KIP2) expression by p73beta. Proc Natl Acad Sci USA. 2002;99:3529–3534
  38. Izzard RA, Jackson SP, Smith GC. Competitive and noncompetitive inhibition of the DNA-dependent protein kinase. Cancer Res. 1999;59:2581–2586
  39. Allen C, Halbrook J, Nickoloff JA. Interactive competition between homologous recombination and non-homologous end joining. Mol Cancer Res. 2003;1:913–920
  40. Nitin N, LaConte LE, Zurkiya O, Hu X, Bao G. Functionalization and peptide-based delivery of magnetic nanoparticles as an intracellular MRI contrast agent. J Biol Inorg Chem. 2004;9:706–712
  41. Llorca O, Pearl LH. Electron microscopy studies on DNA recognition by DNA-PK. Micron. 2004;35:625–633
  42. Junop MS, Modesti M, Guarne A, Ghirlando R, Gellert M, Yang W. Crystal structure of the Xrcc4 DNA repair protein and implications for end joining. EMBO J. 2000;19:5962–5970
  43. Bladen CL, Udayakumar D, Takeda Y, Dynan WS. Identification of the polypyrimidine tract binding protein-associated splicing factor. p54(nrb) complex as a candidate DNA double-strand break rejoining factor. J Biol Chem. 2005;280:5205–5210
  44. Rappsilber J, Ryder U, Lamond AI, Mann M. Large-scale proteomic analysis of the human spliceosome. Genome Res. 2002;12:1231–1245
  45. Andersen JS, Lyon CE, Fox AH, Leung AK, Lam YW, Steen H, et al. Directed proteomic analysis of the human nucleolus. Curr Biol. 2002;12:1–11
  46. Woodard RL, Lee K, Huang J, Dynan WS. Distinct roles for Ku protein in transcriptional reinitiation and DNA repair. J Biol Chem. 2001;276:15423–15433
  47. Mo X, Dynan WS. Subnuclear localization of Ku protein: functional association with RNA polymerase II elongation sites. Mol Cell Biol. 2002;22:8088–8099
  48. Gnatt AL, Cramer P, Fu J, Bushnell DA, Kornberg RD. Structural basis of transcription: an RNA polymerase II elongation complex at 3.3 Å resolution. Science. 2001;292:1876–1882
  49. Urnov FD, Miller JC, Lee YL, Beausejour CM, Rock JM, Augustus S, et al. Highly efficient endogenous human gene correction using designed zinc-finger nucleases. Nature. 2005;435:646–651
  50. Sadofsky MJ. The RAG proteins in V(D)J recombination: more than just a nuclease. Nucleic Acids Res. 2001;29:1399–1409

 Conflict of Interest: Intellectual property described in this article has been licensed by the Medical College of Georgia to Apeliotus Technologies, 1456 North Morningside Drive, NE, Atlanta GA 30306. WSD is a consultant for Apeliotus Technologies.

 This work was supported by U.S. Public Health Service awards GM 35866 and CA 98239 and by the U.S. Department of Energy Low-Dose Radiation Research Program award DE-FG02-03ER63649. W.S.D. received additional support as an Eminent Scholar of the Georgia Research Alliance.

PII: S1549-9634(06)00044-X

doi: 10.1016/j.nano.2006.04.004

Nanomedicine: Nanotechnology, Biology and Medicine
Volume 2, Issue 2 , Pages 74-81 , June 2006