NUDT1
Description
The NUDT1 (nudix hydrolase 1) is a protein-coding gene located on chromosome 7.
NUDT1 (also known as 2-hydroxy-dATP diphosphatase, oxidized purine nucleoside triphosphatase, (2'-deoxy) ribonucleoside 5'-triphosphate pyrophosphohydrolase, Nudix hydrolase 1, MutT homolog 1, or 7,8-dihydro-8-oxoguanine triphosphatase) is an enzyme that is crucial for DNA repair. It hydrolyzes oxidized purines, preventing their incorporation into the DNA chain, thus playing a critical role in aging and cancer development. NUDT1 catalyzes the following reaction: 2-hydroxy-dATP + H2O ⇌ 2-hydroxy-dAMP + diphosphate The enzyme hydrolyzes oxidized purine nucleoside triphosphates, such as 8-oxo-dGTP, 8-oxo-dATP, 2-oxo-dATP, 2-hydroxy-dATP, and 2-hydroxy rATP, to monophosphates. This prevents misincorporation of these oxidized nucleotides into DNA and/or RNA during replication and transcription, which could lead to mutations causing carcinogenesis or neurodegeneration. NUDT1 was first identified in Escherichia coli for its ability to prevent the incorporation of 8-oxoguanine into DNA. In contrast to MutT enzymes in other organisms, which often exhibit substrate specificity for certain types of oxidized nucleotides (like E. coli, which is specific to 8-oxoguanine nucleotides), human MTH1 (NUDT1) has a broader specificity for a wide range of oxidatively damaged nucleotides. This broad specificity stems from the recognition of these nucleotides in the enzyme's substrate binding pocket, facilitated by an exchange of protonation state between two nearby aspartate residues.
NUDT1, also known as Oxidized purine nucleoside triphosphate hydrolase, is a crucial enzyme involved in maintaining the integrity of the nucleotide pool by removing oxidized and methylated nucleotides. It catalyzes the hydrolysis of 2-oxo-dATP (2-hydroxy-dATP) into 2-oxo-dAMP and exhibits significant hydrolase activity towards 2-oxo-ATP, 8-oxo-dGTP, and 8-oxo-dATP. By preventing the incorporation of these damaged nucleotides into DNA, NUDT1 safeguards against mutations, particularly transversions such as A:T to C:G and G:C to T:A, which can lead to cancer and other diseases. Furthermore, NUDT1 hydrolyzes methylated purine nucleoside triphosphates, further contributing to its antimutagenic activity and protecting cells from oxidative stress.
NUDT1 is also known as MTH1.
