Journal Article

Potentially Lethal Damage Repair in Drug Arrested G2-Phase Cells after Radiation Exposure

Genik, Paula C., Maeda, Junko, Brents, Colleen A., Kato, Takamitsu A., Genet, Matthew D., Fujii, Yoshihiro, Bell, Justin J., Genet, Stefan C.

2014

Overview

Potentially lethal damage (PLD) repair has been defined as that property conferring the ability of cells to recover from DNA damage depending on the postirradiation environment. Using a novel cyclin dependent kinase 1 inhibitor RO-3306 to arrest cells in the G2 phase of the cell cycle, examined PLD repair in G2 in cultured Chinese hamster ovary (CHO) cells. Several CHO-derived DNA repair mutant cell lines were used in this study to elucidate the mechanism of DNA double-strand break repair and to examine PLD repair during the G2 phase of the cell cycle. While arrested in G2 phase, wild-type CHO cells displayed significant PLD repair and improved cell survival compared with cells released immediately from G2 after irradiation. Both the radiation-induced chromosomal aberrations and the delayed entry into mitosis were also reduced by G2-holding PLD recovery. The PLD repair observed in G2 was observed in nonhomologous end-joining (NHEJ) mutant cell lines but absent in homologous recombination mutant cell lines. From the survival curves, G2-NHEJ mutant cell lines were found to be very sensitive to gamma-ray exposure when compared to G2/homologous recombination mutant cell lines. Our findings suggest that after exposure to ionizing radiation during G2, NHEJ is responsible for the majority of non-PLD repair, and conversely, that the homologous recombination is responsible for PLD repair in G2.

• Publisher: The Radiation Research Society,Radiation Research Society
• Subject: Animals / Cell culture techniques / Cell cycle / Cell lines / CHO Cells / Cricetinae / Cricetulus / Cytogenetic Analysis / DNA Damage / DNA End-Joining Repair - drug effects / DNA End-Joining Repair - genetics / DNA End-Joining Repair - radiation effects / DNA repair / G2 Phase Cell Cycle Checkpoints - drug effects / G2 Phase Cell Cycle Checkpoints - radiation effects / Gamma Rays - adverse effects / Homologous recombination / Irradiation / Rad51 Recombinase - metabolism / Radiation damage / Radiation dosage / REGULAR ARTICLES / X-Rays - adverse effects