Chen Cai, Zheng Yaqi, Gao Tian, Chen Min, Dong Kunming, Shen Li, Bai Yanchao, Zhang Likui
College of Environmental Science and Engineering, Yangzhou University, China.
The Key Laboratory of the Jiangsu Higher Education Institutions for Integrated Traditional Chinese, Western Medicine in Senile Diseases Control, Institute of Translational Medicine, School of Medicine, Yangzhou University, Yangzhou 225001, PR China.
Int J Biol Macromol. 2025 Apr;299:140137. doi: 10.1016/j.ijbiomac.2025.140137. Epub 2025 Jan 20.
Base deamination can lead to DNA base damage, among which cytosine deamination to uracil occurs frequently. Before repair, replication of uracil in DNA will generate GC → AT transversion mutation. Since base deamination is accelerated by high temperature, genomic DNA stability of hyperthermophiles, which grow optimally above 75 °C, is facing a severe threat by the elevated base deamination created by their living high temperature environments. To counteract its potentially harmful effect, cells have employed several pathways for DNA uracil repair, among which base excision repair (BER) is one of major pathways. Uracil DNA glycosylase (UDG) is the first enzyme that initiates BER by excising uracil from DNA. Based on their sequence similarities, UDGs have been divided into six families, among which families IV and V members are predominantly found in hyperthermophiles. Besides, two novel UDGs have been reported from hyperthermophiles. Generally, UDGs from hyperthermophiles exhibit biochemical and structural characteristics distinct from other family UDG members, thereby enriching functional diversity of UDGs. Herein, we have reviewed structure and function of UDGs from hyperthermophiles to provide insights into DNA uracil repair mechanisms, focusing on difference between UDGs from various hyperthermophiles, and difference between archaeal UDGs and bacterial homologs.
碱基脱氨基会导致DNA碱基损伤，其中胞嘧啶脱氨基形成尿嘧啶的情况较为常见。在修复之前，DNA中尿嘧啶的复制会产生GC→AT颠换突变。由于高温会加速碱基脱氨基，最佳生长温度在75°C以上的嗜热菌的基因组DNA稳定性因其高温生存环境导致的碱基脱氨基增加而面临严重威胁。为了抵消其潜在的有害影响，细胞采用了多种DNA尿嘧啶修复途径，其中碱基切除修复（BER）是主要途径之一。尿嘧啶DNA糖基化酶（UDG）是通过从DNA中切除尿嘧啶来启动BER的第一种酶。基于它们的序列相似性，UDG被分为六个家族，其中IV和V家族成员主要存在于嗜热菌中。此外，从嗜热菌中还报道了两种新型UDG。一般来说，嗜热菌中的UDG表现出与其他家族UDG成员不同的生化和结构特征，从而丰富了UDG的功能多样性。在此，我们综述了嗜热菌中UDG的结构和功能，以深入了解DNA尿嘧啶修复机制，重点关注不同嗜热菌中UDG的差异，以及古菌UDG与细菌同源物之间的差异。
