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PNAS:细胞周期中嘌呤合成新机制

来源:生物谷 2015-02-09 10:10

                                                                 

2015年2月9日讯  /生物谷BIOON/  --近日,来自美国的科学家在著名国际期刊PNAS发表一项最新研究成果,他们发现 purinosome的组装与去组装过程随细胞周期变化并且与细胞周期过程中嘌呤的生物合成过程有关,并且在不同细胞模型中purinosome可能出现在细胞周期的不同阶段。
 
研究人员指出,嘌呤从头合成途径需要6个酶的作用,催化磷酸核糖焦磷酸生成5`-磷酸肌苷。在嘌呤缺失的情况下,这些酶能够形成一个多酶复合物,称为purinosome。之前研究已经发现purinosome对哺乳动物癌细胞具有重要作用。在这项研究中,研究人员应用延时荧光显微镜在两个细胞模型中研究细胞周期对purinosome的依赖性。在嘌呤缺失的Hela细胞中发现,许多细胞在G1期形成了purinosome,这一结果得到了细胞同步化的进一步证实。HGPRT缺失的成纤维细胞也在G1期形成大量purinosome,但在S期和G2/M期也出现了purinosome水平上升。在这两种细胞模型中发现细胞周期对purinosome形成存在依赖性,同时这两种细胞模型的结果差异可能是由于嘌呤合成机制不同造成的。
 
综上所述,该文章发现purinosome形成与细胞周期进程密切相关,purinosome可能通过嘌呤从头合成途径发挥功能,响应细胞对嘌呤的需求,并作为细胞代谢流增加的标记。(生物谷Bioon.com)
 
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Purinosome formation as a function of the cell cycle
 
Chung Yu Chana,1, Hong Zhaob,1, Raymond J. Pughb, Anthony M. Pedleyb, Jarrod Frenchc, Sara A. Jonesd,Xiaowei Zhuange, Hyder Jinnahf, Tony Jun Huanga, and Stephen J. Benkovicb,2
 
The de novo purine biosynthetic pathway relies on six enzymes to catalyze the conversion of phosphoribosylpyrophosphate to inosine 5′-monophosphate. Under purine-depleted conditions, these enzymes form a multienzyme complex known as the purinosome. Previous studies have revealed the spatial organization and importance of the purinosome within mammalian cancer cells. In this study, time-lapse fluorescence microscopy was used to investigate the cell cycle dependency on purinosome formation in two cell models. Results in HeLa cells under purine-depleted conditions demonstrated a significantly higher number of cells with purinosomes in the G1 phase, which was further confirmed by cell synchronization. HGPRT-deficient fibroblast cells also exhibited the greatest purinosome formation in the G1 phase; however, elevated levels of purinosomes were also observed in the S and G2/M phases. The observed variation in cell cycle-dependent purinosome formation between the two cell models tested can be attributed to differences in purine biosynthetic mechanisms. Our results demonstrate that purinosome formation is closely related to the cell cycle.
 
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