Division of Neurofunctional Genomics, Department of Immunobiology and Neuroscience, Medical Institute of Bioregulation, Kyushu University, Higashi-ku, Fukuoka, Japan.
Nucleic Acids Res. 2010 Aug;38(14):4834-43. doi: 10.1093/nar/gkq249. Epub 2010 Apr 12.
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.
核苷酸在各种生物反应中发挥作用；然而，它们可以经历各种化学修饰。如果不从核苷酸池中去除这些修饰的核苷酸，它们可能对细胞有毒。我们进行了修饰核苷酸结合蛋白的筛选，并鉴定出人核苷酸二磷酸连接部分 X 型基序 16（NUDT16）蛋白为肌苷三磷酸（ITP）/黄苷三磷酸（XTP）/GTP 结合蛋白。重组 NUDT16 将嘌呤核苷二磷酸水解为相应的核苷一磷酸。在所检查的 29 种核苷酸中，最高的 k(cat)/K(m) 值为肌苷二磷酸（IDP）和脱氧肌苷二磷酸（dIDP）。此外，NUDT16 适度水解（脱氧）肌苷三磷酸([d]ITP)。NUDT16 主要定位于细胞核，特别是核仁。在 HeLa MR 细胞中敲低 NUDT16 会导致细胞周期停滞在 S 期，降低细胞增殖，增加核 DNA 中单链断裂的积累以及 RNA 中肌苷的水平增加。因此，我们得出结论，NUDT16 是一种（脱氧）肌苷二磷酸酶，可能主要在核内发挥作用，以保护细胞免受（d）ITP 的有害影响。
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