Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 310-315 , September 2009

Backup pathways of NHEJ in cells of higher eukaryotes: Cell cycle dependence

  • George Iliakis

      Affiliations

    • Corresponding Author InformationAddress: Institute of Medical Radiation Biology, University of Duisburg-Essen Medical School, Hufelandstrasse 55, 45122 Essen, Germany.

Received 15 May 2009 ,Revised 9 June 2009 ,Accepted 24 June 2009.

References 

  1. Thompson LH, Limoli CL. Origin, recognition, signaling, and repair of DNA double-strand breaks in mammalian cells. Eurekah.com and Kluwer Academic/Plenum Publishers; 2003;
  2. West SC. Molecular views of recombination proteins and their control. Nat Rev Mol Cell Biol. 2003;4:1–11
  3. Lieber MR, Ma Y, Pannicke U, Schwarz K. Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol. 2003;4:712–720
  4. Valerie K, Povirk LF. Regulation and mechanisms of mammalian double-strand break repair. Oncogene. 2003;22:5792–5812
  5. Paques F, Haber JE. Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev. 1999;63:349–404
  6. Symington LS. Role of Rad52 epistasis group genes in homologous recombination and double-strand break repair. Microbiol Mol Biol Rev: MMBR. 2002;66:630–670
  7. Georgakilas AG. Processing of DNA damage clusters in human cells: current status of knowledge. Mol BioSyst. 2008;4:30–35
  8. Singh SK, Wu W, Wu W, Wang M, Iliakis G. Extensive repair of DNA double-strand breaks in cells deficient in the DNA-PK dependent pathway of NHEJ after exclusion of heat-labile sites. Radiat Res 2009;172.doi:1667/RR1745.1661.
  9. Stenerlöw B, Karlsson KH, Cooper B, Rydberg B. Measurement of prompt DNA double-strand breaks in mammalian cells without including heat-labile sites: results for cells deficient in nonhomologous end joining. Radiat Res. 2003;159:502–510
  10. Kinner A, Wu W, Staudt C, Iliakis G. G-H2AX in recognition and signaling of DNA double-strand breaks in the context of chromatin. Nucleic Acids Res. 2008;36:5678–5694
  11. Jeggo PA, Löbrich M. Artemis links ATM to double strand break rejoining. Cell Cycle 2005;4:e42–4.
  12. Löbrich M, Jeggo PA. The impact of a negligent G2/M checkpoint on genomic instability and cancer induction. Nat Rev Cancer. 2007;7:861–869
  13. Dahm-Daphi J, Dikomey E. Rejoining of DNA double-strand breaks in X-irradiated CHO cells studied by constant- and graded-field gel electrophoresis. Int J Radiat Biol. 1996;69:615–621
  14. Rothkamm K, Krüger I, Thompson LH, Löbrich M. Pathways of DNA double-strand break repair during the mammalian cell cycle. Mol Cell Biol. 2003;23:5706–5715
  15. DiBiase SJ, Zeng Z-C, Chen R, Hyslop T, Curran WJ, Iliakis G. DNA-dependent protein kinase stimulates an independently active, nonhomologous, end-joining apparatus. Cancer Res. 2000;60:1245–1253
  16. Lieber MR, Ma Y, Pannicke U, Schwarz K. The mechanism of vertebrate nonhomologous DNA end joining and its role in V(D)J recombination. DNA Repair (Amst) 2004;3:817–26.
  17. Wang H, Zeng Z-C, Bui T-A, et al. Efficient rejoining of radiation-induced DNA double-strand breaks in vertebrate cells deficient in genes of the RAD52 epistasis group. Oncogene. 2001;20:2212–2224
  18. Wang H, Zhao-Chong Z, Perrault AR, Cheng X, Qin W, Iliakis G. Genetic evidence for the involvement of DNA ligase IV in the DNA-PK-dependent pathway of non-homologous end joining in mammalian cells. Nucleic Acids Res. 2001;29:1653–1660
  19. Terzoudi GI, Singh SK, Pantelias GE, Iliakis G. Premature chromosome condensation reveals DNA-PK independent pathways of chromosome break repair. Int J Oncol. 2008;31:145–152
  20. Bezzubova OY, Buerstedde J-M. Gene conversion in the chicken immunoglobulin locus: a paradigm of homologous recombination in higher eukaryotes. Experientia. 1994;50:270–276
  21. Buerstedde J-M, Takeda S. Increased ratio of targeted to random integration after transfection of chicken B cell lines. Cell. 1991;67:179–188
  22. Sonoda E, Sasaki MS, Buerstedde J-M. Et al. Rad51-deficient vertebrate cells accumulate chromosomal breaks prior to cell death. EMBO J. 1998;17:598–608
  23. Löbrich M, Rydberg B, Cooper PK. Repair of x-ray-induced DNA double-strand breaks in specific NotI restriction fragments in human fibroblasts: joining of correct and incorrect ends. Proc Natl Acad Sci USA. 1995;92:12050–12054
  24. Wang H, Perrault AR, Takeda Y, Qin W, Wang H, Iliakis G. Biochemical evidence for Ku-independent backup pathways of NHEJ. Nucleic Acids Res. 2003;31:5377–5388
  25. Cheong N, Perrault AR, Wang H. Et al. DNA-PK-independent rejoining of DNA double-strand breaks in human cell extracts in vitro. Int J Radiat Biol. 1999;75:67–81
  26. Perrault R, Wang H, Wang M, Rosidi B, Iliakis G. Backup pathways of NHEJ are suppressed by DNA-PK. J Cell Biochem. 2004;92:781–794
  27. Ellenberger T, Tomkinson AE. Eukaryotic DNA ligases: structural and functional insights. Annu Rev Biochem. 2008;77:313–338
  28. Wang H, Rosidi B, Perrault R, et al. DNA ligase III as a candidate component of backup pathways of nonhomologous end joining. Cancer Res. 2005;65:4020–4030
  29. Windhofer F, Wu W, Iliakis G. Low levels of DNA ligases III and IV sufficient for effective NHEJ. J Cell Physiol. 2007;213:475–483
  30. Puebla-Osorio N, Lacey DB, Alt FW, Zhu C. Early embryonic lethality due to targeted inactivation of DNA ligase III. Mol Cell Biol. 2006;26:3935–3941
  31. Wang M, Wu W, Wu W, et al. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006;34:6170–6182
  32. Audebert M, Salles B, Calsou P. Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining. J Biol Chem. 2004;279:55117–55126
  33. Audebert M, Salles B, Weinfeld M, Calsou P. Involvement of polynucleotide kinase in a poly(ADP-ribose) polymerase-1-dependent DNA double-strand breaks rejoining pathway. J Mol Biol. 2006;356:257–265
  34. Audebert M, Calsou P. Effect of double-strand break DNA sequence on the PARP-1 NHEJ pathway. Biochem Biophys Res Commun. 2008;369:982–988
  35. Rosidi B, Wang M, Wu W, Sharma A, Wang H, Iliakis G. Histone H1 functions as a stimulatory factor in backup pathways of NHEJ. Nucleic Acids Res. 2008;36:1610–1623
  36. Wu W, Wang M, Wu W, Singh SK, Mussfeldt T, Iliakis G. Repair of radiation induced DNA double strand breaks by backup NHEJ is enhanced in G2. DNA Repair (Amst) 2008;7:329–38.
  37. Wu W, Wang M, Mussfeldt T, Iliakis G. Enhanced use of backup pathways of NHEJ in G2 in Chinese hamster mutant cells with defects in the classical pathway of NHEJ. Radiat Res. 2008;170:512–520
  38. Windhofer F, Wu W, Wang M, et al. Marked dependence on growth state of backup pathways of NHEJ. Int J Radiat Oncol Biol Phys. 2007;68:1462–1470
  39. Rodemann HP, Dittmann K, Toulany M. Radiation-induced EGFR-signaling and control of DNA-damage repair. Int J Radiat Biol. 2007;83:781–791
  40. Asaad NA, Zeng Z-C, Guan J, Thacker J, Iliakis G. Homologous recombination as a potential target for caffeine radiosensitization in mammalian cells: reduced caffeine radiosensitization in XRCC2 and XRCC3 mutants. Oncogene. 2000;19:5788–5800
  41. Xia F, Taghian DG, DeFrank JS, Zeng Z-C, Willers H, Iliakis G. Deficiency of human BRCA2 leads to impaired homologous recombination but maintains normal nonhomologous end joining. Proc Natl Acad Sci USA. 2001;98:8644–8649
  42. Bennett RAO, Gu X-Y, Povirk LF. Construction of a vector containing a site-specific DNA double-strand break with 3′-phosphoglycolate termini and analysis of the products of end-joining in CV-1 cells. Int J Radiat Biol. 1996;70:

PII: S0167-8140(09)00335-1

doi: 10.1016/j.radonc.2009.06.024

Radiotherapy & Oncology
Volume 92, Issue 3 , Pages 310-315 , September 2009

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