NUDT1 prevents the misincorporation of oxidized nucleotides during replication and transcription, thereby mitigating oxidative DNA damage (ODD) . This is critical in:
Cancer cells: High NUDT1 expression counteracts MYC-driven reactive oxygen species (ROS) production, enabling survival under oxidative stress .
Aging: Overexpression in mice reduces 8-oxoguanine levels in DNA, correlating with a 16% lifespan extension .
MYC-PLK1 Axis: MYC overexpression induces PLK1-mediated phosphorylation of NUDT1, enhancing its enzymatic activity without altering protein levels .
FOXM1 Dependency: In pulmonary arterial hypertension (PAH), FOXM1 upregulates NUDT1 to protect against oxidative damage .
NUDT1 is overexpressed in aggressive cancers, including:
NUDT1-null mice exhibit elevated 8-oxo-dGTP and accelerated aging, while overexpression delays oxidative damage accumulation .
Controversies: Early inhibitors like TH588 showed promise, but later studies (e.g., AstraZeneca, MD Anderson) reported limited efficacy, questioning NUDT1’s validity as a target .
NUDT1 serves as a biomarker in:
MGSSHHHHHH SSGLVPRGSH MGASRLYTLV LVLQPQRVLL GMKKRGFGAG RWNGFGGKVQ EGETIEDGAR RELQEESGLT VDALHKVGQI VFEFVGEPEL MDVHVFCTDS IQGTPVESDE MRPCWFQLDQ IPFKDMWPDD SYWFPLLLQK KKFHGYFKFQ GQDTILDYTL REVDTV.
NUDT1 hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP and 8-oxo-dATP, into their corresponding monophosphates. This activity prevents the incorporation of these oxidized nucleotides into DNA, which could otherwise lead to mutations and genomic instability . The enzyme is predominantly found in the cytoplasm, with some presence in the mitochondria, indicating its role in sanitizing nucleotide pools for both nuclear and mitochondrial genomes .
The human recombinant form of NUDT1 is typically produced in Escherichia coli and is a single, non-glycosylated polypeptide chain containing 176 amino acids. It is often fused with a 20 amino acid His tag at the N-terminus to facilitate purification . The enzyme has a molecular mass of approximately 20.1 kDa .
The recombinant NUDT1 is purified using proprietary chromatographic techniques to achieve a purity greater than 95%, as determined by SDS-PAGE . The enzyme is formulated in a solution containing Tris-HCl buffer, glycerol, dithiothreitol (DTT), and sodium chloride (NaCl) to ensure stability and activity .