A historical reflection on our understanding of radiation-induced DNA double strand break repair in somatic mammalian cells; interfacing the past with the present.

Purpose: The International Journal of Radiation Biology (IJRB) is celebrating 60 years of publishing in 2019. IJRB has made an enormous contribution to publishing papers that have enhanced our understanding of the DNA damage response (DDR) activated following exposure to ionizing radiation (IR). The IR-induced DDR field has a rich history but many outstanding papers pass unread by young scientists overwhelmed by the current literature. We provide a historical reflection on key advances in the DDR field and interface them with current knowledge. Conclusions: DNA double strand breaks (DSBs) were identified as the major biological lesion induced by IR. But early studies on cells from IR-sensitive ataxia telangiectasia patients showed that DSB repair was not sufficient to prevent IR hypersensitivity. Subsequently, the ATM-dependent signal transduction process was revealed, with the breadth of the response being slowly unearthed. Early studies demonstrated at least two processes of DSB repair and revealed that mis-repair causes translocation formation. Recent studies, however, are unraveling more complexity in the repair process, including the specific processing of DSBs within transcriptionally active regions, and the significance of the chromatin environment. Despite the quality of these early and current studies, many questions remain to be addressed.