A Molecular Dynamics of Radiation-Induced DNA Damage Response: Exploring the Pathways of Signaling, Repair, and Cell Death

Abstract

Purpose: In this review, we summarized the latest information related to accidentally and/or un-accidental exposure of ionizing radiation triggered by oxidative stress and/or cytotoxicity and adverse effects on human health such as hematopoietic, gastrointestinal and cerebrovascular injury collectively referred to as acute radiation syndromes. Directly or indirectly IR induced oxidation of biomolecules, especially DNA, resulting in altered genomic stability and DNA strand breaks. DNA strand breaks are recognized by DNA damage sensory protein that activates downstream checkpoint kinases as well as initiate compensatory multiple intracellular and intranuclear signaling pathways, resulting in cell cycle arrest and DNA repair. Simultaneously activates tumor suppressor genes leading to death signaling pathway or triggering of numerous autocrine/paracrine loops leading to structural dis-organization and programmed cell death. These signaling pathways work together to decrease the magnitude of radiotherapy and promote the development of radiation resistance in cancer cells. The fate of the cells and DNA damage repair depending on the severity of radiation exposure and types of DNA damage. Conclusions: Based on the recent invested reports related to IR and DNA damage signaling, this review would be helpful for researchers and healthcare providers to develop a new research concept and translate this information into a cancer therapeutic approach. Moreover, target specific screening and development of radiation countermeasures agent for radiological emergencies.