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.

中文翻译：

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分子放射生物学和碱基切除修复途径的起源：一个历史视角

摘要

目的

为了证明分子放射生物学家对能够识别和消除电离辐射产生的 DNA 损伤的酶的搜索是如何与碱基切除修复途径的发展交织在一起的。

结论

碱基切除修复途径可修复绝大多数辐射引起的 DNA 损伤，包括碱基损伤、碱不稳定损伤和单链断裂。事实证明，碱基切除修复实际上进化为每天修复我们每个细胞中形成的大约三十到四万个内源性损伤。因此，这个过程非常有效，因此，在相对低剂量的辐射下，通过碱基切除修复修复的单个损伤几乎不会导致致命或致突变事件。这种效率是一把双刃剑，因为沿辐射轨道产生的电离辐射诱导的羟基自由基在 DNA 中形成双链和串联簇损伤。这些损伤被有效的碱基切除修复酶识别，在尝试修复过程中，导致双链断裂和/或可使复制叉坍塌的多重损伤。与修复孤立损伤的相对容易性和效率相比，由电离辐射形成的双链断裂和其他复杂或成簇损伤对 DNA 修复系统提出了截然不同的挑战。