NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
Nucleotides function in a variety of biological reactions; however, they can undergo various chemical modifications. Such modified nucleotides may be toxic to cells if not eliminated from the nucleotide pools. We performed a screen for modified-nucleotide binding proteins and identified human nucleoside diphosphate linked moiety X-type motif 16 (NUDT16) protein as an inosine triphosphate (ITP)/xanthosine triphosphate (XTP)/GTP-binding protein. Recombinant NUDT16 hydrolyzes purine nucleoside diphosphates to the corresponding nucleoside monophosphates. Among 29 nucleotides examined, the highest k(cat)/K(m) values were for inosine diphosphate (IDP) and deoxyinosine diphosphate (dIDP). Moreover, NUDT16 moderately hydrolyzes (deoxy)inosine triphosphate ([d]ITP). NUDT16 is mostly localized in the nucleus, and especially in the nucleolus. Knockdown of NUDT16 in HeLa MR cells caused cell cycle arrest in S-phase, reduced cell proliferation, increased accumulation of single-strand breaks in nuclear DNA as well as increased levels of inosine in RNA. We thus concluded that NUDT16 is a (deoxy)inosine diphosphatase that may function mainly in the nucleus to protect cells from deleterious effects of (d)ITP.
Iyama
Teruaki
T
Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Abolhassani
Nona
N
Tsuchimoto
Daisuke
D
Nonaka
Mari
M
Nakabeppu
Yusaku
Y
D017766:Acid Anhydride Hydrolases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D002467:Cell Nucleus / Q000737:chemistry; D049109:Cell Proliferation; D053904:DNA Breaks, Single-Stranded; D055785:Gene Knockdown Techniques; D006160:Guanosine Triphosphate / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D007292:Inosine Nucleotides / Q000378:metabolism; D007293:Inosine Triphosphate / Q000378:metabolism; D008969:Molecular Sequence Data; D011755:Pyrophosphatases / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D012265:Ribonucleotides / Q000378:metabolism
D007292:Inosine Nucleotides; D012265:Ribonucleotides; D007293:Inosine Triphosphate; C065326:xanthosine 5'-triphosphate; D006160:Guanosine Triphosphate; D017766:Acid Anhydride Hydrolases; C523314:Nudt16 protein, human; D011755:Pyrophosphatases; C021446:inosine diphosphatase
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