NTHL1 Human

hNTH1 is an iron-sulfur (Fe-S) cluster-containing enzyme. The Fe-S cluster plays a significant role in the enzyme’s function, particularly in recognizing and binding to damaged DNA sites. The enzyme has both DNA glycosylase and AP-lyase activities:

1. DNA Glycosylase Activity: This activity allows hNTH1 to recognize and remove damaged bases from DNA by cleaving the N-glycosidic bond, leaving behind an apurinic/apyrimidinic (AP) site .
2. AP-Lyase Activity: Following the removal of the damaged base, the AP-lyase activity cleaves the phosphodiester bond at the AP site through a beta-elimination reaction .

hNTH1 is essential for maintaining genome integrity. Mutations in the nth1 gene, which encodes hNTH1, have been associated with the development of adenomatous polyposis and colorectal cancer . The enzyme’s ability to repair oxidative damage helps prevent mutations that could lead to cancer and other genetic disorders.

Comparative studies between human and bacterial Endonuclease III (EndoIII) have shown that while they share similar catalytic domains, hNTH1 has an additional N-terminal domain (NTD) consisting of approximately 90 amino acids . This NTD is believed to be important for DNA binding and damage recognition. The three-dimensional structure of hNTH1, particularly the N-terminally truncated form, has provided insights into its unique domain organization and flexibility .

Recombinant hNTH1 is widely used in research to study DNA repair mechanisms and to develop therapeutic strategies for diseases caused by oxidative DNA damage. The enzyme is typically produced in bacterial systems, such as Escherichia coli, and purified for use in various biochemical assays .