锥虫有六种线粒体DNA解旋酶，其中一种控制动质体大环复制。
Trypanosomes have six mitochondrial DNA helicases with one controlling kinetoplast maxicircle replication.
作者信息
Liu Beiyu, Wang Jianyang, Yaffe Nurit, Lindsay Megan E, Zhao Zhixing, Zick Aviad, Shlomai Joseph, Englund Paul T
机构信息
Department of Biological Chemistry, Johns Hopkins Medical School, Baltimore, MD 21205, USA.
出版信息
Mol Cell. 2009 Aug 28;35(4):490-501. doi: 10.1016/j.molcel.2009.07.004. Epub 2009 Jul 30.
Kinetoplast DNA (kDNA), the trypanosome mitochondrial DNA, contains thousands of minicircles and dozens of maxicircles interlocked in a giant network. Remarkably, Trypanosoma brucei's genome encodes 8 PIF1-like helicases, 6 of which are mitochondrial. We now show that TbPIF2 is essential for maxicircle replication. Maxicircle abundance is controlled by TbPIF2 level, as RNAi of this helicase caused maxicircle loss, and its overexpression caused a 3- to 6-fold increase in maxicircle abundance. This regulation of maxicircle level is mediated by the TbHslVU protease. Previous experiments demonstrated that RNAi knockdown of TbHslVU dramatically increased abundance of minicircles and maxicircles, presumably because a positive regulator of their synthesis escaped proteolysis and allowed synthesis to continue. Here, we found that TbPIF2 level increases following RNAi of the protease. Therefore, this helicase is a TbHslVU substrate and an example of a positive regulator, thus providing a molecular mechanism for controlling maxicircle replication.
动质体DNA（kDNA），即锥虫的线粒体DNA，包含数千个小环和数十个大环，它们相互连锁形成一个巨大的网络。值得注意的是，布氏锥虫的基因组编码8种PIF1样解旋酶，其中6种存在于线粒体中。我们现在表明，TbPIF2对大环复制至关重要。大环丰度受TbPIF2水平控制，因为对这种解旋酶进行RNA干扰会导致大环丢失，而其过表达会使大环丰度增加3至6倍。大环水平的这种调节由TbHslVU蛋白酶介导。先前的实验表明，对TbHslVU进行RNA干扰会显著增加小环和大环的丰度，推测是因为它们合成的一个正调节因子逃脱了蛋白水解作用，从而使合成得以继续。在这里，我们发现蛋白酶的RNA干扰后TbPIF2水平会升高。因此，这种解旋酶是TbHslVU的底物，也是一个正调节因子的例子，从而为控制大环复制提供了一种分子机制。
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