MUTM E.Coli

Fpg is classified as a bifunctional DNA glycosylase with both N-glycosylase and apurinic/apyrimidinic (AP) lyase activities . The enzyme contains a zinc-finger motif near its C-terminal, which is essential for its DNA-binding and catalytic activities .

Fpg recognizes and excises oxidatively damaged purines, such as 8-oxo-7,8-dihydroguanine (8-oxoG) and 2,6-diamino-4-hydroxy-5-formamidopyrimidine (FapyG) . The N-glycosylase activity of Fpg cleaves the N-glycosidic bond, releasing the damaged base and creating an AP site. The AP lyase activity then cleaves the DNA backbone at the AP site via β- and δ-elimination, resulting in a single-nucleotide gap with 3’ and 5’ phosphate termini .

In E. coli, the expression of Fpg is regulated by the soxRS and oxyR regulons, which are activated in response to oxidative stress . The recombinant form of Fpg is typically expressed in E. coli strains engineered to overproduce the enzyme for research and industrial applications .

The primary function of Fpg is to protect cells from the mutagenic effects of oxidative DNA damage. By excising damaged bases and initiating the BER pathway, Fpg helps maintain the integrity of the genetic material . This process is vital for preventing mutations that could lead to various diseases, including cancer.

The activity of Fpg is tightly regulated by cellular oxidative stress levels. The soxRS and oxyR regulons control the transcription of the fpg gene, ensuring that the enzyme is produced in response to increased oxidative damage . Additionally, post-translational modifications and interactions with other DNA repair proteins may further modulate Fpg activity.

Recombinant Fpg is widely used in research to study DNA repair mechanisms and to assess oxidative DNA damage in various experimental systems . Its ability to recognize and excise specific damaged bases makes it a valuable tool for understanding the molecular basis of DNA repair and the effects of oxidative stress on genomic stability.