Down-regulation of PERK enhances resistance to ionizing radiation

Abstract

Although, ionizing radiation (IR) has been implicated to cause stress in endoplasmic reticulum (ER), how ER stress signaling and major ER stress sensors modulate cellular response to IR is unclear. Protein kinase RNA-like endoplasmic reticulum kinase (PERK) is an ER transmembrane protein which initiates unfolded protein response (UPR) or ER stress signaling when ER homeostasis is disturbed. Here, we report that down-regulation of PERK resulted in increased clonogenic survival, enhanced DNA repair and reduced apoptosis in irradiated cancer cells. Our study demonstrated that PERK has a role in sensitizing cancer cells to IR.

Keywords: DDR; DDSBs; DNA damage; DNA damage response; DNA double strand breaks; ER-stress; IR; Ionizing radiation; PERK; SDS–PAGE; ionizing radiation; sodium dodecyl sulfate–polyacrylamide gel electrophoresis.