Hwang Yuna, Kang Su-Jin, Kang Jieun, Choi Jeongwoo, Kim Seung-Jin, Jang Sunbok
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
Graduate Program in Innovative Biomaterials Convergence, Ewha Womans University, Seoul, Republic of Korea.
Exp Mol Med. 2025 Mar;57(3):524-532. doi: 10.1038/s12276-025-01417-0. Epub 2025 Mar 3.
The base excision repair pathway protects DNA from base damage via oxidation, deamination, alkylation and methylation. DNA glycosylases are key enzymes that recognize damaged bases in a lesion-specific manner and initiate the base excision repair process. Among these, the endonuclease VIII-like 1-3 (NEIL1-3) family, which is found in mammalian genomes, is a homolog of bacterial DNA glycosylases known as Fpg/Nei. NEIL enzymes have similar structures and substrates but with slight differences. When repair proteins are impaired, the accumulation of damaged bases can lead to increased genomic instability, which is implicated in various pathologies, including cancer and neurodegeneration. Notably, mutations in these proteins also influence a range of other diseases and inflammation. This review focuses on the influence of the NEIL family on human health across different organ systems. Investigating the relationship between NEIL mutations and diseases can improve our understanding of how these enzymes affect the human body. This information is crucial for understanding the basic mechanisms of DNA repair and enabling the development of novel inhibitors or gene therapies that target only these enzymes. Understanding the role of the NEIL family provides insights into novel therapies and improves our ability to combat genetic diseases.
碱基切除修复途径通过氧化、脱氨、烷基化和甲基化保护DNA免受碱基损伤。DNA糖基化酶是以损伤特异性方式识别受损碱基并启动碱基切除修复过程的关键酶。其中，存在于哺乳动物基因组中的核酸内切酶VIII样1-3（NEIL1-3）家族是细菌DNA糖基化酶Fpg/Nei的同源物。NEIL酶具有相似的结构和底物，但存在细微差异。当修复蛋白受损时，受损碱基的积累会导致基因组不稳定性增加，这与包括癌症和神经退行性变在内的各种病理状况有关。值得注意的是，这些蛋白的突变也会影响一系列其他疾病和炎症。本综述重点关注NEIL家族对不同器官系统中人类健康的影响。研究NEIL突变与疾病之间的关系可以增进我们对这些酶如何影响人体的理解。这些信息对于理解DNA修复的基本机制以及开发仅靶向这些酶的新型抑制剂或基因疗法至关重要。了解NEIL家族的作用有助于深入了解新型疗法，并提高我们对抗遗传疾病的能力。
