Lowered nudix type 5 (NUDT5) expression leads to cell cycle retardation in HeLa cells.
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.
Graduate School, Peking Union Medical College & Chinese Academy of Medical Sciences, Beijing 100730, People's Republic of China.
Li-Qun
LQ
Zhang
Da-Peng
DP
Dai
Wei
W
Gan
Yasumitsu
Y
Takagi
Hiroshi
H
Hayakawa
Mutsuo
M
Sekiguchi
Jian-Ping
JP
Cai
D017209:Apoptosis; D049109:Cell Proliferation; D002470:Cell Survival; D015536:Down-Regulation; D005260:Female; D059585:G1 Phase Cell Cycle Checkpoints; D015972:Gene Expression Regulation, Neoplastic; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D006868:Hydrolysis; D010084:Oxidation-Reduction; D011755:Pyrophosphatases / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012334:RNA, Neoplasm / Q000378:metabolism; D002583:Uterine Cervical Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D012334:RNA, Neoplasm; C024829:8-hydroxyguanine; D006147:Guanine; C403715:NUDT5 protein, human; D011755:Pyrophosphatases