Abstract
Ionizing radiations induce DNA DSBs to the genome. Cell cycling is then suppressed by the damage responsible checkpoints from which cell-cycle progression are released only after completion of DSB repair. Interestingly however, descendants of the damaged cells are prone to exhibit delayed genomic instability in eukaryotes, suggesting a memory of the damage whose mechanism is poorly understood. We have studied delayed recombination in the fission yeast Schizosaccharomyces pombe to investigate its molecular mechanism. X-irradiation increased recombination frequency of a marker with 200 bp tandem repeats dose dependently from 1.0x10-2% to ~10x10-2% at a dose of 500 Gy and the elevated frequency persisted for at least 8-10 cell generations. Production of ROS and other bystander factors were not involved in the delayed recombination. In addition, a single DSB in the genome was found to induce recombination in trans at a site elsewhere in the genome. In parallel to the elevated recombination, Rad22 (a Rad52 homologue) focus persisted in the irradiated cells for 10 generations after irradiation. Comparison of expression profiling by HiCEP revealed that at least 45 transcripts exhibited changes in their expression level along with the delayed recombination and that more than 100 transcripts changed their expression level at least 13 generations. These results indicate that damage is memorized by cell even after completion of repair of damage and that genome-wide change of transcription and activation of recombination machinery operate at the downstream of the memory mechanism.
