Radiation-induced DNA repair foci: Spatio-temporal aspects of formation, application for assessment of radiosensitivity and biological dosimetry

Several proteins involved in DNA repair and DNA damage signaling have been shown to produce discrete foci in response to ionizing radiation. These foci are believed to co-localize to DSB and referred to as ionizing radiation-induced foci (IRIF) or DNA repair foci.Recent studies have revealed that some residual IRIF remain in cells for a relatively long time after irradiation, and have indicated a possible correlation between radiosensitivity of cells and residual IRIF. Remarkably, residual foci are significantly larger in size than the initial foci. Increase in the size of IRIF with time upon irradiation has been found in various cell types and has partially been correlated with dynamics and fusion of initial foci.Although it is admitted that the number of IRIF reflect that of DSB, several studies report a lack of correlation between kinetics for IRIF and DSB and a lack of co-localization between DSB repair proteins. These studies suggest that some proportion of residual IRIF that depend on cell type, dose, and post-irradiation time may represent alternations in chromatin structure after DSB have been repaired or misrepaired. While precise functions of residual foci are presently unknown, their possible link to remaining chromatin alternations, nuclear matrix, apoptosis, delayed repair and misrejoining of DSB, activity of several kinases, phosphatases, and checkpoint signaling has been suggested. Another intriguing possibility is that some of DNA repair foci may mark break-points at chromosomal aberrations (CA). While this possibility has not been confirmed substantially, the residual foci seem to be useful for biological dosimetry and estimation of individual radiosensitivity in radiotherapy of cancer.