MPG Human

N-Methylpurine-DNA glycosylase (MPG), also known as 3-methyladenine-DNA glycosylase, is a crucial enzyme in the base excision repair (BER) pathway. This enzyme is responsible for recognizing and excising damaged bases from DNA, specifically those induced by alkylating and oxidizing agents .

MPG plays a pivotal role in maintaining genomic stability by removing alkylated and deaminated purines from DNA. The enzyme recognizes and excises a variety of damaged bases, including hypoxanthine, xanthine, uracil, and thymine . The excision of these bases is the first step in the BER pathway, which is essential for repairing DNA damage and preventing mutations .

The intrinsic kinetic parameters (kcat and Km) for the excision of hypoxanthine by the recombinant human MPG protein have been determined, revealing that the differences in specificity are primarily in product release rather than binding . The MPG protein forms a strong complex with the product of excision, an abasic site, as well as with a reduced abasic site .

MPG is a monofunctional glycosylase, meaning it only performs the glycosylase activity without associated lyase activity. The enzyme binds to damaged DNA and cleaves the N-glycosidic bond, releasing the damaged base and leaving an abasic site . The MPG protein protects a specific region of the DNA strand, indicating a precise interaction with its target .

The removal of damaged bases by MPG is critical for preventing cytotoxicity and mutagenesis. Alkylating agents, a subclass of DNA-damaging agents, introduce N-methylpurines into DNA, which can be cytotoxic or premutagenic if left unrepaired . By excising these damaged bases, MPG helps to maintain the integrity of the genome and prevent the accumulation of mutations .

Mutations or deficiencies in the MPG gene can lead to various diseases, including Laurence-Moon syndrome and chronic granulomatous disease . Understanding the function and mechanism of MPG is essential for developing therapeutic strategies to address these conditions.