NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
NUDT16 is a (deoxy)inosine diphosphatase, and its deficiency induces accumulation of single-strand breaks in nuclear DNA and growth arrest.
复制标题
DOI：
10.1093/nar/gkq249
复制
发表时间：
2010-08
影响因子：
14.9
通讯作者：
Nakabeppu Y
中科院分区：
文献类型：
--
作者：
Iyama T;Abolhassani N;Tsuchimoto D;Nonaka M;Nakabeppu Y
核苷酸在各种生物反应中发挥作用；然而，它们可以进行各种化学修饰。这种修饰的核苷酸如果不从核苷酸池中消除，可能会对细胞产生毒性。我们对修饰核苷酸结合蛋白进行了筛选，发现人核苷二磷酸连接部分X-型基序16(NUDT16)蛋白是一个三磷酸肌苷(ITP)/三磷酸黄苷(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。在所检测的29个核苷酸中，kcat/kM值最高的是肌苷二磷酸(IDP)和脱氧肌苷二磷酸(DIDP)。此外，NUDT16适度地水解(脱氧)三磷酸肌苷([d]ITP)。NUDT16主要定位于细胞核，尤其是核仁。在HeLa MR细胞中，NUDT16基因被敲除后，细胞周期停滞在S期，细胞增殖受阻，核DNA单链断裂增多，核糖核酸中肌苷水平升高。因此，我们得出结论，NUDT16是一种(脱氧)肌苷二磷酸酶，可能主要在细胞核内发挥作用，以保护细胞免受(D)ITP的有害影响。
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 kcat/Km 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.
登录
查看更多内容
影响因子：
2.9
作者：
Lee, Chun-Yue I.;Delaney, James C.;Kartalou, Maria;Lingaraju, Gondichatnahalli M.;Maor-Shoshani, Ayelet;Essigmann, John M.;Samson, Leona D.
通讯作者：
Samson, Leona D.
影响因子：
5.4
作者：
Nonaka, Mari;Tsuchimoto, Daisuke;Nakabeppu, Yusaku
通讯作者：
Nakabeppu, Yusaku
影响因子：
9
作者：
Nakamura, Atsushi;Watanabe, Shinji;Katagiri, Shigeru
通讯作者：
Katagiri, Shigeru
影响因子：
4.8
作者：
Lin, SR;McLennan, AG;Mao, YM
通讯作者：
Mao, YM
影响因子：
14.9
作者：
MYRNES, B;GUDDAL, PH;KROKAN, H
通讯作者：
KROKAN, H