Abstract:Thymine glycol (Tg) is one of the common oxidative DNA damage bases. It can stall DNA polymerase and RNA polymerase that perform DNA replication and transcription, thus leading to the termination of the corresponding biological processes and further causing cell death. Therefore, Tg in DNA needs to be repaired. Endonuclease Ⅲ (EndoⅢ) is a bifunctional DNA glycosylase capable of excising Tg from DNA, thus initiating a base excision repair pathway for restoring Tg to a normal T base. The genomes of bacteria, archaea, and eukaryotes possess the gene encoding EndoⅢ. The available studies mainly focus on the EndoⅢ in bacteria and eukaryotes while rarely concern archaeal EndoⅢ. We reviewed the research progress on the EndoⅢ in hyperthermophilic archaea and proposed the future research directions in this field.