O6-methylguanine-DNA methyltransferase (MGMT or AGT) is a DNA repair protein with the capability to remove alkyl groups from O6-AlkylG adducts. Moreover, MGMT plays a crucial role in repairing DNA damage induced by methylating agents like temozolomide and chloroethylating agents such as carmustine, and thereby contributes to chemotherapeutic resistance when these agents are used. This review delves into the structural roles and repair mechanisms of MGMT, with emphasis on the potential structural and functional roles of the N-terminal domain of MGMT. It also explores the development of cancer therapeutic strategies that target MGMT. Finally, it discusses the intriguing crosstalk between MGMT and other DNA repair pathways.
O6-甲基鸟嘌呤-DNA甲基转移酶（MGMT或AGT）是一种能够从O6-烷基鸟嘌呤加合物中移除烷基的DNA修复蛋白。此外，MGMT在修复由替莫唑胺等甲基化剂以及卡莫司汀等氯乙基化剂诱导的DNA损伤中发挥关键作用，因此当使用这些药物时，MGMT会促进化疗耐药性的产生。本综述深入探讨了MGMT的结构作用与修复机制，重点关注其N端结构域潜在的结构与功能角色。同时，文章还探索了针对MGMT的癌症治疗策略的发展。最后，文中讨论了MGMT与其他DNA修复通路之间引人关注的交互作用。
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