Cellular Responses to Ionizing Radiation: Mechanisms of DNA Repair and Mutation

Abstract

Ionizing radiation (IR) induces various cellular responses that significantly impact DNA integrity, triggering a cascade of mechanisms aimed at repairing damage and maintaining genomic stability. DNA can suffer different types of damage from IR, including single-strand breaks (SSBs), double-strand breaks (DSBs), and base modifications. Cellular responses involve intricate repair pathways such as base excision repair (BER), nucleotide excision repair (NER), and homologous recombination (HR), which work to restore genetic fidelity. When DNA repair mechanisms are overwhelmed or erroneous, mutations can arise, influencing cell function and potentially leading to carcinogenesis. Cells possess complex signaling pathways, such as the p53 tumor suppressor pathway, that regulate the cell cycle and apoptosis in response to severe damage, thereby influencing cell fate and survival.
Despite these sophisticated reparative processes, not all radiation-induced DNA damage is corrected. Mutagenesis can occur if repair mechanisms fail or if errors are introduced during repair, leading to permanent changes in the DNA sequence. These mutations can manifest in various forms, including point mutations, insertions, deletions, and chromosomal rearrangements. The accumulation of such mutations in critical genes related to cell cycle control and apoptosis can contribute to the development of cancer over time. Understanding the precise mechanisms by which cells respond to ionizing radiation is crucial for improving radiotherapy strategies, developing protective measures, and assessing cancer risk associated with environmental exposure to radiation.