Repair of potentially lethal damage in normal cells and ataxia telangiectasia cells; consideration of non-homologous end-joining

Momoe Kan'o, Tetsuya Kawata, Hisao Ito, Naoyuki Shigematsu, Cuihua Liu, Takashi Uno, Kouich Isobe, Hiroyuki Kawakami, Francis Cucinotta, Kerry George, Atsushi Kubo

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

When cell lines are held in a quiescent state after irradiation, survival rates are greater than those from cells that are stimulated to grow immediately after irradiation. These differences in survival rates correspond to rates of potentially lethal damage repair. The effects of confluent holding recovery after γ-irradiation were investigated using normal human fibroblasts (AG1522) and ataxia telangiectasia fibroblasts (GM02052). Calyculin-A-induced premature chromosome condensation and fluorescent in situ hybridization were applied to study G2/M chromosomal aberrations. Survival results indicated normal capacity for PLDR in AG1522 cells but that PLDR was extremely compromised in GM02052 cells. The chromosomal aberration frequency decreased when AG1522 cells were allowed to repair for 24-h, whereas 24-hour incubation had little effect on the aberration frequency in GM02052 cells. Since the main mechanism for dsbs repair during G0/G1 phases of the cells cycle involve the non-homologous end-joining (NHEJ) process, our study indicates that for AG1522 cells the NHEJ repair process is more likely to induce accurate chromosome repair under quiescent G0 conditions than proliferating G1 phase, while in GM02052 cells the fidelity of NHEJ is similarly defective at either cell cycle phase. Reduced fidelity of NHEJ may be responsible for PLDR defect and its hyper- radiosensitivity in A-T cells.

Original languageEnglish
Pages (from-to)31-38
Number of pages8
JournalJournal of radiation research
Volume48
Issue number1
DOIs
Publication statusPublished - 2007

Keywords

  • Chromosome aberrations
  • FISH (fluorescence in situ hybridization)
  • Misrepair
  • NHEJ (non-homologous end-joining)
  • PLDR (potentially lethal damage repair)

ASJC Scopus subject areas

  • Radiation
  • Radiology Nuclear Medicine and imaging
  • Health, Toxicology and Mutagenesis

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