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Lowered Nudix type 5 (NUDT5) expression leads to cell cycle retardation in HeLa cells

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Abstract

The molecule 8-oxo-7,8-dihydroguanine (8-oxoGua), an oxidized form of guanine, can pair with adenine or cytosine during nucleic acid synthesis. Moreover, RNA containing 8-oxoGua causes translational errors, thus leading to the production of abnormal proteins. Human NUDT5, a MutT-related protein, catalyzes the hydrolysis of 8-oxoGDP to 8-oxoGMP, thereby preventing misincorporation of 8-oxoGua into RNA. To investigate the biological roles of NUDT5 in mammalian cells, we established cell lines with decreased level of NUDT5 expression. In NUDT5 inhibited cells, the RNA oxidation was not significantly higher than that of normal cells. However, the cell cycle G1 phase was significantly delayed, and cell numbers in both S and G2/M phases were reduced, indicating that cell proliferation was hampered by NUDT5 suppression. Key proteins for preventing the G1-S transition, including p53, p16, and Rb were increased, while the Rb phosphorylation was decreased. These results suggested that the NUDT5 protein may play significant roles in regulating the G1-S transition in mammalian cells.

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Acknowledgments

This study was supported by the Key International Science and Technology Cooperation Projects (2006DFB31410). We thank Dr. Ping Jiang for advice and assistance. There is no conflict of interest.

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Authors and Affiliations

  1. Graduate School, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China

    Li-Qun Zhang & Wei Gan

  2. National Center for Clinical Laboratory, Beijing Hospital, Ministry of Health, No. 1, Da Hua Road, Dong Dan, Beijing, 100730, People’s Republic of China

    Li-Qun Zhang & Wei Gan

  3. The Key Laboratory of Geriatrics, Beijing Hospital & Beijing Institute of Geriatrics, Ministry of Health, No. 1, Da Hua Road, Dong Dan, Beijing, 100730, People’s Republic of China

    Da-Peng Dai & Jian-Ping Cai

  4. Frontier Research Center, Fukuoka Dental College, Fukuoka, 814-0193, Japan

    Yasumitsu Takagi, Hiroshi Hayakawa & Mutsuo Sekiguchi

Authors
  1. Li-Qun Zhang
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  2. Da-Peng Dai
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  3. Wei Gan
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  4. Yasumitsu Takagi
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  5. Hiroshi Hayakawa
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  6. Mutsuo Sekiguchi
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  7. Jian-Ping Cai
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Correspondence to Jian-Ping Cai.

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Zhang, LQ., Dai, DP., Gan, W. et al. Lowered Nudix type 5 (NUDT5) expression leads to cell cycle retardation in HeLa cells. Mol Cell Biochem 363, 377–384 (2012). https://doi.org/10.1007/s11010-011-1190-x

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  • DOI: https://doi.org/10.1007/s11010-011-1190-x

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