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  • Title: Molecular radiobiology and the origins of the base excision repair pathway: an historical perspective.
    Author: Wallace SS.
    Journal: Int J Radiat Biol; 2023; 99(6):891-902. PubMed ID: 33787444.
    Abstract:
    PURPOSE: To demonstrate how the search by the Molecular Radiobiologists for enzymes that could recognize and remove DNA damage produced by ionizing radiation was intertwined with the development of the Base Excision Repair pathway. CONCLUSION: The Base Excision Repair pathway repairs the vast majority of radiation-induced DNA damages including base damages, alkali labile lesions, and single strand breaks. It turns out that Base Excision Repair actually evolved to repair some thirty to forty thousand endogenous lesions formed in each of our cells every day. Thus, this process is extremely efficient and accordingly, at relatively low doses of radiation, the single lesions repaired by base excision repair result in few lethal or mutagenic events. This efficiency is a double-edged sword since ionizing radiation-induced hydroxyl radicals produced along the radiation track form both bistranded and tandem clustered lesions in DNA. These damages are recognized by the efficient Base Excision Repair enzymes, which, during attempted repair, lead to double strand breaks and/or multiple lesions that can collapse replication forks. Double strand breaks and other complex or clustered lesions formed by ionizing radiation present distinct challenges to DNA repair systems compared to the relative ease and efficiency by which isolated lesions are repaired.
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