title: Potentially lethal damage repair in drug arrested G2-phase cells after radiation exposure.
abstract: 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.
authors.affiliation: a  Department of Environmental and Radiological Health Sciences, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, Colorado, 80523.
authors.forename: Junko
authors.initials: J
authors.lastname: Maeda
authors.forename: Justin J
authors.initials: JJ
authors.lastname: Bell
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Genet
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fujii
authors.forename: Matthew D
authors.initials: MD
authors.lastname: Genet
authors.forename: Colleen A
authors.initials: CA
authors.lastname: Brents
authors.forename: Paula C
authors.initials: PC
authors.lastname: Genik
authors.forename: Takamitsu A
authors.initials: TA
authors.lastname: Kato
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D020732:Cytogenetic Analysis; D004249:DNA Damage; D059766:DNA End-Joining Repair / Q000187:drug effects / Q000235:genetics / Q000528:radiation effects*; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects* / Q000528:radiation effects*; D005720:Gamma Rays / Q000009:adverse effects; D051135:Rad51 Recombinase / Q000378:metabolism; D014965:X-Rays / Q000009:adverse effects
chemical_list: D051135:Rad51 Recombinase