Roy Shreya, Azhar Md Khabeer, Gupta Vibha
Department of Biotechnology, Jaypee Institute of Information Technology, A-10 Sec 62, Noida, 201309, India.
Current Affiliation- Center of Computational Natural Science and Bioinformatics, International Institute of Information Technology, Hyderabad, 500032, India.
Protein Pept Lett. 2025;32(2):85-96. doi: 10.2174/0109298665318621241128041145.
Endogenous or exogenous DNA damage needs to be repaired, therefore, cells in all the three domains have repair pathways to maintain the integrity of their genetic material. Uracil DNA glycosylases (UDGs), also known as UNGs (uracil-DNA N-glycosylases), are part of the base-excision repair (BER) pathway. These enzymes specifically remove uracil from DNA molecules by cleaving the glycosidic bond between the uracil base and the deoxyribose sugar. UDGs can be broadly classified into six families, and each of them share conserved motifs that are critical for substrate recognition and catalysis. Recently, an unconventional UDG known as UDGX has been identified from the species , which is different from other UDG members in forming an irreversible and extremely stable complex with DNA that is resistant to even harsh denaturants such as SDS, NaOH, and heat. This suicide inactivation mechanism prevents uracil excision and might play a protective role in maintaining genome integrity, as bacterial survival under hypoxic conditions is reduced due to the overexpression of MsmUDGX. Additionally, due to the importance of UDGs, the number of structures has been resolved. Moreover, high-resolution 3D structures of apo MsmUDGX, as well as uracil and DNAbound forms, are available in PDB. This review aims to provide insights into the specific structural- functional aspects of each UDG family member for theragnostic applications.
内源性或外源性DNA损伤都需要修复，因此，所有三个域中的细胞都有修复途径来维持其遗传物质的完整性。尿嘧啶DNA糖基化酶（UDGs），也称为UNG（尿嘧啶-DNA N-糖基化酶），是碱基切除修复（BER）途径的一部分。这些酶通过切割尿嘧啶碱基与脱氧核糖之间的糖苷键，特异性地从DNA分子中去除尿嘧啶。UDGs可大致分为六个家族，每个家族都有保守基序，这些基序对于底物识别和催化至关重要。最近，从该物种中鉴定出一种非传统的UDG，称为UDGX，它与其他UDG成员不同，能与DNA形成不可逆且极其稳定的复合物，甚至能抵抗SDS、NaOH和热等苛刻变性剂。这种自杀失活机制阻止了尿嘧啶切除，可能在维持基因组完整性方面发挥保护作用，因为由于MsmUDGX的过表达，缺氧条件下细菌的存活率降低。此外，由于UDGs的重要性，已有多个结构得到解析。此外，apo MsmUDGX以及与尿嘧啶和DNA结合形式的高分辨率3D结构可在蛋白质数据银行（PDB）中获取。本综述旨在深入探讨每个UDG家族成员在治疗诊断应用中的特定结构-功能方面。
