Potentially Lethal Damage Repair in Drug Arrested G(2)-Phase Cells after Radiation Exposure

作者：Maeda Junko; Bell Justin J; Genet Stefan C; Fujii Yoshihiro; Genet Matthew D; Brents Colleen A; Genik Paula C; Kato Takamitsu A^*

来源：Radiation Research, 2014, 182(4): 448-457.

DOI：10.1667/RR13744.1

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

• 出版日期2014-10