Effects of targeted phosphorylation site mutations in the DNA-PKcs phosphorylation domain on low and high LET radiation sensitivity

Ian M. Cartwright, Justin J. Bell, Junko Maeda, Matthew D. Genet, Ashley Romero, Yoshihiro Fujii, Akira Fujimori, Hisashi Kitamuta, Tadashi Kamada, David J. Chen, Takamitsu A. Kato

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The present study investigated the effect of targeted mutations in the DNA-dependent protein kinase catalytic subunit and phosphorylation domains on the survival of cells in response to different qualities of ionizing radiation. Mutated Chinese hamster ovary V3 cells were exposed to 500 MeV/nucleon initial energy and 200 keV/μm monoenergetic Fe ions; 290 MeV/nucleon initial energy and average 50 keV/μm spread-out Bragg peak C ions; 70 MeV/nucleon initial energy and 1 keV/μm monoenergetic protons; and 0.663 MeV initial energy and 0.3 keV/μm Cs137 γ radiation. The results demonstrated that sensitivity to high linear energy transfer radiation is increased when both S2056 and T2609 clusters each contain a point mutation or multiple mutations are present in either cluster, whereas the phosphoinositide 3 kinase cluster only requires a single mutation to induce the sensitized phenotype of V3 cells. Additionally, the present study demonstrated that sensitivity to DNA cross-linking damage by cisplatin only requires a single mutation in one of the three clusters and that additional point mutations do not increase cell sensitivity.

Original languageEnglish (US)
Pages (from-to)1621-1627
Number of pages7
JournalOncology Letters
Volume9
Issue number4
DOIs
StatePublished - 2015

Fingerprint

Linear Energy Transfer
Radiation Tolerance
Phosphorylation
Mutation
DNA
Point Mutation
DNA-Activated Protein Kinase
Ions
Radiation
1-Phosphatidylinositol 4-Kinase
Cricetulus
Ionizing Radiation
Cisplatin
Protons
Ovary
Catalytic Domain
Cell Survival
Phenotype
Nucleons

Keywords

  • DNA-protein kinase catalytic subunit
  • Heavy ions
  • High linear energy transfer radiation
  • Protons

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cartwright, I. M., Bell, J. J., Maeda, J., Genet, M. D., Romero, A., Fujii, Y., ... Kato, T. A. (2015). Effects of targeted phosphorylation site mutations in the DNA-PKcs phosphorylation domain on low and high LET radiation sensitivity. Oncology Letters, 9(4), 1621-1627. https://doi.org/10.3892/ol.2015.2974

Effects of targeted phosphorylation site mutations in the DNA-PKcs phosphorylation domain on low and high LET radiation sensitivity. / Cartwright, Ian M.; Bell, Justin J.; Maeda, Junko; Genet, Matthew D.; Romero, Ashley; Fujii, Yoshihiro; Fujimori, Akira; Kitamuta, Hisashi; Kamada, Tadashi; Chen, David J.; Kato, Takamitsu A.

In: Oncology Letters, Vol. 9, No. 4, 2015, p. 1621-1627.

Research output: Contribution to journalArticle

Cartwright, IM, Bell, JJ, Maeda, J, Genet, MD, Romero, A, Fujii, Y, Fujimori, A, Kitamuta, H, Kamada, T, Chen, DJ & Kato, TA 2015, 'Effects of targeted phosphorylation site mutations in the DNA-PKcs phosphorylation domain on low and high LET radiation sensitivity', Oncology Letters, vol. 9, no. 4, pp. 1621-1627. https://doi.org/10.3892/ol.2015.2974
Cartwright, Ian M. ; Bell, Justin J. ; Maeda, Junko ; Genet, Matthew D. ; Romero, Ashley ; Fujii, Yoshihiro ; Fujimori, Akira ; Kitamuta, Hisashi ; Kamada, Tadashi ; Chen, David J. ; Kato, Takamitsu A. / Effects of targeted phosphorylation site mutations in the DNA-PKcs phosphorylation domain on low and high LET radiation sensitivity. In: Oncology Letters. 2015 ; Vol. 9, No. 4. pp. 1621-1627.
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