Genomic DNA is chemically reactive and therefore susceptible to damage by many exogenous and endogenous sources. Lesions produced from these damaging events can have various mutagenic and genotoxic consequences. This Perspective follows the journey of one particular lesion, 1,N⁶-ethenoadenine (εA), from its formation to replication and repair, and its role in cancerous tissues and inflammatory diseases. εA is generated by the reaction of adenine (A) with vinyl chloride or lipid peroxidation products. We present the miscoding properties of εA with an emphasis on how bacterial and mammalian cells can process lesions differently, leading to varied mutational spectra. But with information from these assays, we can better understand how the miscoding properties of εA lead to biological consequences and how genomic stability can be maintained via DNA repair mechanisms. We discuss how base excision repair (BER) and direct reversal repair (DRR) can minimize the biological consequences of εA lesions. Kinetic parameters of glycosylases and AlkB family enzymes are described, along with a discussion of the relative contributions of the BER and DRR pathways in the repair of εA. Because eukaryotic DNA is packaged in chromatin, we also discuss the impact of this packaging on BER and DRR, specifically in regards to repair of εA. Studying DNA lesions like εA in this context, from origin to biological implications, can provide crucial information to better understand prevention of mutagenesis and cancer.

中文翻译：

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1,N6-Ethenoadenine：从分子到生物学后果†

基因组 DNA 具有化学反应性，因此容易受到许多外源和内源来源的损害。由这些破坏性事件产生的损伤可能具有各种诱变和基因毒性后果。这个视角跟随一个特定病变的旅程，1，N ⁶- 乙烯腺嘌呤 (εA)，从其形成到复制和修复，以及它在癌组织和炎症性疾病中的作用。εA 由腺嘌呤 (A) 与氯乙烯或脂质过氧化产物反应生成。我们介绍了 εA 的错误编码特性，重点是细菌和哺乳动物细胞如何以不同的方式处理病变，从而导致不同的突变谱。但是通过这些分析的信息，我们可以更好地了解 εA 的错误编码特性如何导致生物学后果以及如何通过 DNA 修复机制维持基因组稳定性。我们讨论了碱基切除修复 (BER) 和直接逆转修复 (DRR) 如何最大限度地减少 εA 病变的生物学后果。描述了糖基化酶和 AlkB 家族酶的动力学参数，以及对 BER 和 DRR 通路在 εA 修复中的相对贡献的讨论。由于真核 DNA 包装在染色质中，我们还讨论了这种包装对 BER 和 DRR 的影响，特别是在 εA 修复方面。在这种情况下研究像 εA 这样的 DNA 损伤，从起源到生物学意义，可以提供重要信息，以更好地了解诱变和癌症的预防。