Cross-Talk Between DNA Damage and Autophagy and Its Implication in Cancer Therapy

Abstract

Chemotherapy and radiotherapy regimens are designed primarily to induce DNA damage to kill cancer cells. DNA damage response (DDR) proteins recognize and repair a variety of DNA damages. In response to DNA damage, a well-orchestrated autophagy program, comprising of than 30 autophagy-related genes (ATG), are triggered to degrade and recycle damaged proteins and cellular components for aiding DNA repair process. Recently, several interesting reports have showed the pivotal role of DDR proteins in regulating dozens of autophagy proteins and vice versa. Cross-talk between these two functionally different cellular processes may immensely contribute towards the understanding of resistance or sensitization of cancer cells in response to chemotherapy and radiotherapy. Nevertheless, the precise molecular link between DDR and autophagy still remains obscure and elusive. In the current review, we provide comprehensive insights into the underlying mechanisms involved in the molecular crosstalk between DDR and autophagy, which differentially regulate cancer cell fate in response to DNA damaging chemotherapeutics and radiotherapeutics or chemotherapy and radiotherapy.