Influence of double-strand-break repair pathways on radiosensitivity throughout the cell cycle in CHO cells

John M. Hinz, N. Alice Yamada, Edmund P. Salazar, Robert S. Tebbs, Larry H. Thompson

Research output: Contribution to journalArticlepeer-review

87 Scopus citations


Unrepaired DNA double-strand breaks (DSBs) produced by ionizing radiation (IR) are a major determinant of cell killing. To determine the contribution of DNA repair pathways to the well-established cell cycle variation in IR sensitivity, we compared the radiosensitivity of wild-type CHO cells to mutant lines defective in nonhomologous end joining (NHEJ), homologous recombination repair (HRR), and the Fanconi anemia pathway. Cells were irradiated with IR doses that killed ∼90% of each asynchronous population, separated into synchronous fractions by centrifugal elutriation, and assayed for survival (colony formation). Wild-type cells had lowest resistance in early G1 and highest resistance in S phase, followed by declining resistance as cells move into G2/M. In contrast, HR-defective cells (xrcc3 mutation) were most resistant in early G1 and became progressively less resistant in S and G2/M, indicating that the S-phase resistance in wild-type cells requires HRR. Cells defective in NHEJ (dna-pkcs mutation) were exquisitely sensitive in early G1, most resistant in S phase, and then somewhat less resistant in G2/M. Fancg mutant cells had almost normal IR sensitivity and normal cell cycle dependence, suggesting that Fancg contributes modestly to survival and in a manner that is independent of cell cycle position.

Original languageEnglish (US)
Pages (from-to)782-792
Number of pages11
JournalDNA Repair
Issue number7
StatePublished - Jul 12 2005
Externally publishedYes


  • Cell synchrony
  • DNA double-strand breaks
  • Fanconi anemia
  • Homologous recombination
  • Nonhomologous end joining

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology


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