Cell cycle-dependent repair of double-strand DNA breaks in a gamma-ray-sensitive Chinese hamster cell.
A Chinese hamster cell mutant has been isolated which is extremely sensitive to killing by gamma-irradiation in the G1 and early S phases of the cell cycle (LD50 of 20 vs. 250 rads for parent), but which has nearly normal resistance in late S. The mutant cell is able to repair single-stranded DNA breaks introduced by gamma-radiation. However, in comparison to its parental cell, the mutant is deficient in the repair of double-stranded DNA breaks produced by gamma-irradiation during the sensitive G1-early S period, while in the resistant late S period, the repair is nearly the same for both cell types. This correlation between gamma-ray sensitivity and repair strongly suggests that an inability to repair double-strand DNA breaks in G1 is the basis for the hypersensitivity of the mutant to killing by gamma-rays in this phase of the cell cycle. It also provides direct evidence in mammalian cells that the ability to repair double-strand DNA breaks induced by ionizing radiation is an important biochemical function in cell survival and supports the hypothesis that unrepaired double-strand breaks are a major lethal lesion in mammalian cells. A plausible explanation for the appearance of the cell cycle phenotype of the mutant is that in normal cells there are at least two pathways for the repair of double-strand breaks, one of which functions primarily in late S phase, and the other, either throughout the cell cycle or only in the G1 and early S phases.
D000818:Animals; D002453:Cell Cycle; D002460:Cell Line; D002470:Cell Survival / Q000528:radiation effects; D006224:Cricetinae; D003412:Cricetulus; D004247:DNA / Q000528:radiation effects*; D004260:DNA Repair / Q000528:radiation effects*; D004277:DNA, Single-Stranded / Q000528:radiation effects; D005260:Female; D005720:Gamma Rays; D009154:Mutation; D010053:Ovary; D010641:Phenotype; D011836:Radiation Tolerance
D004277:DNA, Single-Stranded; D004247:DNA