Archaeal DNA alkylation repair conducted by DNA glycosylase and methyltransferase

Alkylated bases in DNA created in the presence of endogenous and exogenous alkylating agents are either cytotoxic or mutagenic, or both to a cell. Currently, cells have evolved several strategies for repairing alkylated base. One strategy is a base excision repair process triggered by a specific DNA glycosylase that is used for the repair of the cytotoxic 3-methyladenine. Additionally, the cytotoxic and mutagenic O-6-methylguanine (O-6-meG) is corrected by O-6-methylguanine methyltransferase (MGMT) via directly transferring the methyl group in the lesion to a specific cysteine in this protein. Furthermore, oxidative DNA demethylation catalyzed by DNA dioxygenase is utilized for repairing the cytotoxic 3-methylcytosine (3-meC) and 1-methyladenine (1-meA) in a direct reversal manner. As the third domain of life, Archaea possess 3-methyladenine DNA glycosylase II (AlkA) and MGMT, but no DNA dioxygenase homologue responsible for oxidative demethylation. Herein, we summarize recent progress in structural and biochemical properties of archaeal AlkA and MGMT to gain a better understanding of archaeal DNA alkylation repair, focusing on similarities and differences between the proteins from different archaeal species and between these archaeal proteins and their bacterial and eukaryotic relatives. To our knowledge, it is the first review on archaeal DNA alkylation repair conducted by DNA glycosylase and methyltransferase.

Automated summary

Alkylated bases in DNA created by alkylating agents can be toxic or mutagenic to cells. Cells use various strategies to repair alkylated bases, such as base excision repair process, direct reversal repair and oxidative DNA demethylation. This review focuses on the structural and biochemical properties of archaeal AlkA and MGMT, comparing them with their bacterial and eukaryotic counterparts. It provides insights into the DNA alkylation repair mechanisms in archaea, especially the first comprehensive review on DNA repair conducted by DNA glycosylase and methyltransferase in archaea.