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

Research output: Contribution to journalArticle

33 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

Fingerprint

Ionizing Radiation
Cell Survival
X-Rays
G1 Phase
Phosphatidylinositol 3-Kinase
DNA Ligases
Double-Stranded DNA Breaks
Homologous Recombination
Genetic Markers
Chromosome Aberrations
DNA Damage
Chickens
Cell Cycle
DNA
Genes
DNA Ligase ATP

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

Cite this

Iwabuchi, K., Hashimoto, M., Matsui, T., Kurihara, T., Shimizu, H., Adachi, N., ... 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

53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis. / Iwabuchi, Kuniyoshi; Hashimoto, Mitsumasa; Matsui, Tadashi; Kurihara, Takayuki; Shimizu, Hiroko; Adachi, Noritaka; Ishiai, Masamichi; Yamamoto, Ken-ichi; Tauchi, Hiroshi; Takata, Minoru; Koyama, Hideki; Date, Takayasu.

In: Genes to Cells, Vol. 11, No. 8, 08.2006, p. 935-948.

Research output: Contribution to journalArticle

Iwabuchi, K, Hashimoto, M, Matsui, T, Kurihara, T, Shimizu, H, Adachi, N, Ishiai, M, Yamamoto, K, 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, vol. 11, no. 8, pp. 935-948. https://doi.org/10.1111/j.1365-2443.2006.00989.x
Iwabuchi, Kuniyoshi ; Hashimoto, Mitsumasa ; Matsui, Tadashi ; Kurihara, Takayuki ; Shimizu, Hiroko ; Adachi, Noritaka ; Ishiai, Masamichi ; Yamamoto, Ken-ichi ; Tauchi, Hiroshi ; Takata, Minoru ; Koyama, Hideki ; Date, Takayasu. / 53BP1 contributes to survival of cells irradiated with X-ray during G1 without Ku70 or Artemis. In: Genes to Cells. 2006 ; Vol. 11, No. 8. pp. 935-948.
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