Involvement of Homologous Recombination in Response to Different Qualities of DNA Damage

Abstract: The present studies aimed at elucidate the role of homologous recombination (HR) for the repair of different qualities of DNA damages and/or changes in chromatin structure induced by a variety of radiation qualities.Radiation qualities used to expose cells in culture ranged from non-ionizing radiation with extremely low frequency (ELF), of energies too low to disrupt chemical or molecular bonds, to radiation qualities with energies able to induce ionizations and break chemical bonds. The ionizing radiation (IR) used was both of low- or high-linear energy transfer (LET) producing a range of ionization densities. The higher the ionization density, the worse the cellular outcome in terms of survival, this can also be described as higher relative biological effectiveness (RBE).Homologous recombination that is involved in the repair of double-strand breaks operates mainly in the S and G2/M-phases of the cell cycle when a sister chromatid with the required homology sequence is available as template. HR is also involved in reinitiating stalled or collapsed replication forks, which may be the main task for this pathway.The data obtained with non-ionizing radiation suggest that ELF exposure may either stimulate or inhibit cell growth depending on the state of the cells in terms of chromatin conformation. Although ELF magnetic fields are not directly capable of inducing DNA breaks, a weak but significant increase in DNA fragmentation was observed. However, no induction of HR was indicated. Neither did ELF increase chromatin loop relaxation.A novel finding presented here is that HR seems to process DSBs produced by high-LET relatively more frequently compared to DSBs produced by low-LET. These results in combination with data suggesting that HR (as well as the fast NHEJ and BER) predominantly operates in open chromatin would indicate that a substantial fraction of DSBs induced by high-LET may also originate from the indirect effect.