Potentially Lethal Damage Repair in Drug Arrested Gsub arrow up approximately Phase Cells after Radiation Exposure

• Published in: Radiation research Vol. 182; no. 4; p. 448
• Main Authors: Maeda, Junko, Bell, Justin J, Genet, Stefan C, Fujii, Yoshihiro, Genet, Matthew D, Brents, Colleen A, Genik, Paula C, Kato, Takamitsu A
• Format: Journal Article
• Language: English
• Published: 01.10.2014
• Subjects: Biotechnology; Damage; Deoxyribonucleic acid; Exposure; Homology; Kinases; Repair; Survival
• ISSN: 0033-7587; 1938-5404

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 G sub( 2) phase of the cell cycle, examined PLD repair in G sub( 2) 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 G sub( 2) phase of the cell cycle. While arrested in G sub( 2) phase, wild-type CHO cells displayed significant PLD repair and improved cell survival compared with cells released immediately from G sub( 2) after irradiation. Both the radiation-induced chromosomal aberrations and the delayed entry into mitosis were also reduced by G sub( 2)-holding PLD recovery. The PLD repair observed in G sub( 2) was observed in nonhomologous end-joining (NHEJ) mutant cell lines but absent in homologous recombination mutant cell lines. From the survival curves, G sub( 2)-NHEJ mutant cell lines were found to be very sensitive to gamma-ray exposure when compared to G sub( 2)/homologous recombination mutant cell lines. Our findings suggest that after exposure to ionizing radiation during G sub( 2), NHEJ is responsible for the majority of non-PLD repair, and conversely, that the homologous recombination is responsible for PLD repair in G sub( 2).