Cell cycle- and dose-dependent effects on mitochondrial DNA copy number variation following irradiation.

Abstract

Cell survival after irradiation depends on the cell cycle at the time of exposure. This has been thought to be due to cell cycle-dependent nuclear DNA damage repair mechanisms. Here we show the relationships between the exposed dose, the cell cycle phase at the time of exposure, and changes in mitochondrial DNA copy numbers (mtDNAcn) after irradiation. We used a fluorescent ubiquitination-based cell cycle indicator (FUCCI), which allows visualization of the cell cycle, and confirmed cell cycle synchronization in human cervical HeLa cells. In synchronous HeLa-FUCCI cells, the mtDNAcn changed with the progression of the cell cycle. Also, G1 phase-synchronized cells showed a dose-dependent increase of mtDNAcn at 48 h after X-ray exposure, while G2 cells showed a dose-dependent increase at 24 h. In addition, S phase-synchronized cells showed a dose-dependent increase at 24 and 48 h after irradiation. These results showed the cell cycle- and dose-dependent effects on mtDNAcn after irradiation, which may shed light on the emerging role of mitochondrial genome and in cell survival.