Abstract
PURPOSE: To provide an updated summary of recent advances in our understanding of the non-canonical roles of apoptotic and DNA double-strand break repair factors in various biological processes, especially in the cellular response to radiotherapy. CONCLUSION: Apoptotic caspases are usually considered as "executioners'' of unwanted or damaged cells or tissues. However, recent studies indicated they play multiple additional, often counterintuitive roles in many biological processes. Similarly, DNA double-strand break (DSB) repair factors were also found to play unexpected roles beyond repairing damaged DNA. In this review, I will summarize key findings on the non-canonical roles of apoptotic and DSB repair factors in disparate biological and pathological processes such as radiation-induced genetic instability and carcinogenesis, wound healing and tissue regeneration, induced pluripotent stem cell induction, spontaneous and stochastic generation of cancer stem cells, and cancer immunotherapy. I believe these findings will usher in more studies in this exciting and rapidly evolving field.