53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis

Kuniyoshi Iwabuchi, Mitsumasa Hashimoto, Tadashi Matsui, Takayuki Kurihara, Hiroko Shimizu, Noritaka Adachi, Masamichi Ishiai, Ken Ichi Yamamoto, Hiroshi Tauchi, Minoru Takata, Hideki Koyama, Takayasu Date

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35 Citations (Scopus)

Abstract

Ionizing radiation (IR) induces a variety of DNA lesions. The most significant lesion is a DNA double-strand break (DSB), which is repaired by homologous recombination or nonhomologous end joining (NHEJ) pathway. Since we previously demonstrated that IR-responsive protein 53BP1 specifically enhances activity of DNA ligase IV, a DNA ligase required for NHEJ, we investigated responses of 53BP1-deficient chicken DT40 cells to IR. 53BP1-deficient cells showed increased sensitivity to X-rays during G1 phase. Although intra-S and G2/M checkpoints were intact, the frequency of isochromatid-type chromosomal aberrations was elevated after irradiation in 53BP1-deficient cells. Furthermore, the disappearance of X-ray-induced γ-H2AX foci, a marker of DNA DSBs, was prolonged in 53BP1-deficient cells. Thus, the elevated X-ray sensitivity in G1 phase cells was attributable to repair defect for IR-induced DNA-damage. Epistasis analysis revealed that 53BP1 plays a role in a pathway distinct from the Ku-dependent and Artemis-dependent NHEJ pathways, but requires DNA ligase IV. Strikingly, disruption of the 53BP1 gene together with inhibition of phosphatidylinositol 3-kinase family by wortmannin completely abolished colony formation by cells irradiated during G1 phase. These results demonstrate that the 53BP1-dependent repair pathway is important for survival of cells irradiated with IR during the G1 phase of the cell cycle.

Original languageEnglish
Pages (from-to)935-948
Number of pages14
JournalGenes to Cells
Volume11
Issue number8
DOIs
Publication statusPublished - Aug 2006
Externally publishedYes

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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    Iwabuchi, K., Hashimoto, M., Matsui, T., Kurihara, T., Shimizu, H., Adachi, N., Ishiai, M., Yamamoto, K. I., Tauchi, H., Takata, M., Koyama, H., & Date, T. (2006). 53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis. Genes to Cells, 11(8), 935-948. https://doi.org/10.1111/j.1365-2443.2006.00989.x