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

Abstract

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.

Keywords:

• DNA double strand break repair
• DNA double strand break signaling
• ionizing radiation
• DNA damage
• DNA non-homologous end-joining
• homologous recombination

Acknowledgements

The authors thank Markus Lobrich for reading the manuscript and providing beneficial feedback.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

PAJ is supported by a grant from the Medical Research Council, UK (grant numbers G1000050 and G0500897). Funding to pay the Open Access publication charges for this article was provided by the Medical Research Council (grant number G0500897). AS is supported by Grants-in-Aid from the Japan Society for the Promotion of Science for KAKENHI (JP17H04713).

Notes on contributors

Atsushi Shibata

Dr. Atsushi Shibata is a senior lecture and principal investigator working for Gunma University in Japan. His research interest is to elucidate molecular mechanisms underlying DNA double strand break repair and signaling. He aims to exploit the knowledge to improve cancer therapy.

Penny Jeggo

Prof. Penny Jeggo is a senior scientist at the Genome Damage and Stability Centre at the University of Sussex, Brighton, UK. She has worked on mechanisms of DNA double strand break repair and damage response signalling, and how they influence the response to exposure to ionising radiation.