Structure and function of the uracil DNA glycosylases from hyperthermophiles: Elucidating DNA uracil repair mechanisms: A review.

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.