MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei.
MCM-BP is required for repression of life-cycle specific genes transcribed by RNA polymerase I in the mammalian infectious form of Trypanosoma brucei.
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DOI：
10.1371/journal.pone.0057001
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Cross GA
中科院分区：
文献类型：
--
作者：
Kim HS;Park SH;Günzl A;Cross GA
布氏锥虫变异体表面糖蛋白（VSG）表达是等位基因排斥的典型实例。而T.布氏锥虫含有> 2，000个VSG基因和VSG假基因，只有一个等位基因在每个感染性锥虫的表面表达，而其他等位基因被抑制。沿着重组VSG转换，等位基因排斥为锥虫提供了一种主要的宿主逃避机制，这种现象称为抗原变异。为了扩展我们对锥虫如何通过VSG的差异表达逃避宿主免疫的理解，我们试图通过在T.使用转座子介导的随机插入诱变的布氏杆菌。一个被识别的基因，我们最初命名为LOS 1，编码一个T。布氏杆菌MCM-Binding Protein（TbMCM-BP）。在这里，我们表明，TbMCM-BP是必不可少的感染性血流形式（BF）锥虫的生存能力，并需要适当的细胞周期进程。TbMCM-BP的串联亲和纯化和质谱分析鉴定了TbMCM-BP的4个亚基（MCM 4-MCM 7）。布氏MCM复合物，一种复制性解旋酶，和MCM 8，一种与TbMCM-BP独特共纯化的亚基。TbMCM-BP不仅是抑制亚端粒VSG所必需的，而且也是沉默生命周期特异性昆虫阶段基因、原环素和原环素相关基因（PAG）所必需的，这些基因通常在BF锥虫中被抑制并由RNA聚合酶I转录。我们的研究揭示了T染色体维持和RNA聚合酶I介导的基因沉默之间的功能联系。布鲁塞。
Trypanosoma brucei variant surface glycoprotein (VSG) expression is a classic example of allelic exclusion. While the genome of T. brucei contains >2,000 VSG genes and VSG pseudogenes, only one allele is expressed at the surface of each infectious trypanosome and the others are repressed. Along with recombinatorial VSG switching, allelic exclusion provides a major host evasion mechanism for trypanosomes, a phenomenon known as antigenic variation. To extend our understanding of how trypanosomes escape host immunity by differential expression of VSGs, we attempted to identify genes that contribute to VSG silencing, by performing a loss-of-silencing screen in T. brucei using a transposon-mediated random insertional mutagenesis. One identified gene, which we initially named LOS1, encodes a T. brucei MCM-Binding Protein (TbMCM-BP). Here we show that TbMCM-BP is essential for viability of infectious bloodstream-form (BF) trypanosome and is required for proper cell-cycle progression. Tandem affinity purification of TbMCM-BP followed by mass spectrometry identified four subunits (MCM4-MCM7) of the T. brucei MCM complex, a replicative helicase, and MCM8, a subunit that is uniquely co-purified with TbMCM-BP. TbMCM-BP is required not only for repression of subtelomeric VSGs but also for silencing of life-cycle specific, insect-stage genes, procyclin and procyclin-associated genes (PAGs), that are normally repressed in BF trypanosomes and are transcribed by RNA polymerase I. Our study uncovers a functional link between chromosome maintenance and RNA pol I-mediated gene silencing in T. brucei.
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DOI：
10.1073/pnas.061487598
发表时间：
2001-03-13
影响因子：
11.1
作者：
DaFonseca, CJ;Shu, F;Zhang, JJ
通讯作者：
Zhang, JJ
影响因子：
4.8
作者：
Hammarton, TC;Clark, J;Mottram, JC
通讯作者：
Mottram, JC
影响因子：
64.5
作者：
HORN, D;CROSS, GAM
通讯作者：
CROSS, GAM
影响因子：
3.6
作者：
Denninger, Viola;Fullbrook, Alexander;Rudenko, Gloria
通讯作者：
Rudenko, Gloria
影响因子：
11.4
作者：
Germe, Thomas;Miller, Kyle;Cooper, Julia Promisel
通讯作者：
Cooper, Julia Promisel