DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals

R. T. Hagelstrom, K. F. Askin, A. J. Williams, L. Ramaiah, C. Desaintes, E. H. Goodwin, R. L. Ullrich, S. M. Bailey

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

The phenomenon by which irradiated cells influence non-irradiated neighboring cells, referred to as the bystander effect (BSE), is not well understood in terms of the underlying pathways involved. We sought to enlighten connections between DNA damage repair and the BSE. Utilizing sister chromatid exchange (SCE) frequencies as a marker of the BSE, we performed cell transfer strategies that enabled us to distinguish between generation versus reception of a bystander signal. We find that DNA-dependent Protein Kinase catalytic subunit (DNA-PKcs) and Ataxia Telangectasia Mutated (ATM) are necessary for the generation of such a bystander signal in normal human cells following gamma (γ)-ray exposure, but are not required for its reception. Importantly, we also show that directly irradiated human cells do not respond to receipt of a bystander signal, helping to explain why the BSE is a low-dose phenomenon. These studies provide the first evidence for a role of the DNA damage response proteins DNA-PKcs and ATM specifically in the generation of a bystander signal and intercellular signaling.

Original languageEnglish (US)
Pages (from-to)6761-6769
Number of pages9
JournalOncogene
Volume27
Issue number53
DOIs
StatePublished - Nov 13 2008
Externally publishedYes

Fingerprint

DNA-Activated Protein Kinase
Bystander Effect
Ataxia
Ionizing Radiation
Catalytic Domain
DNA Damage
Sister Chromatid Exchange
Gamma Rays
DNA Repair
Proteins

Keywords

  • ATM
  • Bystander effect
  • DNA-PKcs
  • Ionizing radiation

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

Cite this

Hagelstrom, R. T., Askin, K. F., Williams, A. J., Ramaiah, L., Desaintes, C., Goodwin, E. H., ... Bailey, S. M. (2008). DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. Oncogene, 27(53), 6761-6769. https://doi.org/10.1038/onc.2008.276

DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. / Hagelstrom, R. T.; Askin, K. F.; Williams, A. J.; Ramaiah, L.; Desaintes, C.; Goodwin, E. H.; Ullrich, R. L.; Bailey, S. M.

In: Oncogene, Vol. 27, No. 53, 13.11.2008, p. 6761-6769.

Research output: Contribution to journalArticle

Hagelstrom, RT, Askin, KF, Williams, AJ, Ramaiah, L, Desaintes, C, Goodwin, EH, Ullrich, RL & Bailey, SM 2008, 'DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals', Oncogene, vol. 27, no. 53, pp. 6761-6769. https://doi.org/10.1038/onc.2008.276
Hagelstrom RT, Askin KF, Williams AJ, Ramaiah L, Desaintes C, Goodwin EH et al. DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. Oncogene. 2008 Nov 13;27(53):6761-6769. https://doi.org/10.1038/onc.2008.276
Hagelstrom, R. T. ; Askin, K. F. ; Williams, A. J. ; Ramaiah, L. ; Desaintes, C. ; Goodwin, E. H. ; Ullrich, R. L. ; Bailey, S. M. / DNA-PKcs and ATM influence generation of ionizing radiation-induced bystander signals. In: Oncogene. 2008 ; Vol. 27, No. 53. pp. 6761-6769.
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