The Role of Telomerase in Radiation-Induced Genomic Instability

Otilia Nuta, Kai Rothkamm, Firouz Darroudi

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Findings from previous studies have suggested that the telomerase system is involved in radiation-induced genomic instability. In this study, we investigated the involvement of telomerase in the development and processing of chromosomal damage at different cell cycle stages after irradiation of human fibroblasts. Several response criteria were investigated, including cell survival, chromosomal damage (using the micronucleus assay), G2-induced chromatid aberrations (using the conventional G2 assay as well as a chemically-induced premature chromosome condensation assay) and DNA double-strand breaks (DSBs; using γ-H2AX, 53BP1 and Rad51) in an isogenic pair of cell lines: BJ human foreskin fibroblasts and BJ1-hTERT, a telomerase-immortalized BJ cell line. To distinguish among G1, S and G2 phase, cells were co-immunostained for CENP-F and cyclin A, which are tightly regulated proteins in the cell cycle. After X-ray irradiation at doses in the range of 0.1-6 Gy, the results showed that for cell survival and micronuclei induction, where the overall effect is dominated by the cells in G1 and S phase, no difference was observed between the two cell types; in contrast, when radiation sensitivity at the G2 stage of the cell cycle was analyzed, a significantly higher number of chromatid-type aberrations (breaks and exchanges), and higher levels of γ-H2AX and of Rad51 foci were observed for the BJ cells compared to the BJ1-hTERT cells. Therefore, it can be concluded that telomerase appears to be involved in DNA DSB repair processes, mainly in the G2 phase. These data, taken overall, reinforce the notion that hTERT or other elements of the telomere/telomerase system may defend chromosome integrity in human fibroblasts by promoting repair in G2 phase of the cell cycle.

Original languageEnglish
Pages (from-to)451-459
Number of pages9
JournalRadiation Research
Volume193
Issue number5
DOIs
Publication statusPublished - May 2020

Keywords

  • Cell Line
  • Cell Survival/radiation effects
  • Fibroblasts/cytology
  • G2 Phase/radiation effects
  • Gamma Rays/adverse effects
  • Genomic Instability/radiation effects
  • Humans
  • Micronucleus Tests
  • Rad51 Recombinase/metabolism
  • S Phase/radiation effects
  • Telomerase/metabolism

Fingerprint

Dive into the research topics of 'The Role of Telomerase in Radiation-Induced Genomic Instability'. Together they form a unique fingerprint.

Cite this