Space and Time in the Universe of the Cell Nucleus after Ionizing Radiation Attacks: A Comparison of Cancer and Non-Cancer Cell Response

Abstract

DNA double-strand breaks (DSBs) are known to be the most serious lesions in irradiated cells. Several protein pathways exist for repair. The mechanisms by which cells determine a specific pathway for repair remain poorly understood. DSB induction and repair can be spatiotemporally monitored by ionizing radiation-induced foci (IRIFs) and the formation of repair complexes. IRIF analyses revealed that DSB formation, repair and misrepair are strongly dependent on the radiation characteristics and the microarchitecture of the chromatin environment. However, the IRIF nano-architecture remains unknown, as does its impact on the decision-making process and follow-up protein recruitment. New insights into the relationship between the physical properties of radiation, environmental chromatin architecture, IRIF architecture and DSB repair mechanisms are presented using single-molecule localization microscopy. Ripley distance statistics and persistent homology calculations have shifted our ability to analyze chromatin and IRIF architectures from imaging to topology and structure calculations. We discuss these approaches for cancer treatment-relevant irradiation processes on selected cell systems and consider whether this “structuromics” can enhance our knowledge about the radiation response.