Cytolethal distending toxin demonstrates genotoxic activity in a yeast model
Cytolethal distending toxin demonstrates genotoxic activity in a yeast model
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DOI：
10.1128/iai.69.9.5752-5759.2001
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发表时间：
2001-09-01
影响因子：
3.1
通讯作者：
Pickett, CL
中科院分区：
文献类型：
--
作者：
Hassane, DC;Lee, RB;Pickett, CL
细胞致死膨胀毒素 (CDT) 是由多种细菌病原体产生的多亚基蛋白，可导致哺乳动物细胞增大、细胞周期停滞和凋亡。虽然它们的功能仍不确定，但最近的研究表明它们可以在哺乳动物细胞中充当细胞内 DNA 酶。在这里，我们建立了一种新的酵母模型来了解 CDT 相关疾病。正如在哺乳动物细胞中所见，酵母中 CdtB 亚基的表达会导致 G(2)/M 停滞。在经过基因改造、缺乏 DNA 损伤检查点控制或通过突变体 Cdk1 持续促进细胞周期进展的酵母中，CdtB 的毒性无法避免，因为 CdtB 会造成永久性损伤，导致活力丧失。最后，我们确定 CDT 很可能是强效基因毒素，正如与 CdtB 表达相关的染色体 DNA 体内降解所表明的那样，这表明 CDT 在细菌中的不同分布表明许多人类病原体具有基因毒性活性。
Cytolethal distending toxins (CDTs) are multisubunit proteins produced by a variety of bacterial pathogens that cause enlargement, cell cycle arrest, and apoptosis in mammalian cells. While their function remains uncertain, recent studies suggest that they can act as intracellular DNases in mammalian cells. Here we establish a novel yeast model for understanding CDT-associated disease. Expression of the CdtB subunit in yeast causes a G(2)/M arrest, as seen in mammalian cells. CdtB toxicity is not circumvented in yeast genetically altered to lack DNA damage checkpoint control or that constitutively promote cell cycle progression via mutant Cdk1, because CdtB causes a permanent type of damage that results in loss of viability. Finally, we establish that CDTs are likely to be potent genotoxins, as indicated by in vivo degradation of chromosomal DNA associated with expression of CdtB-suggesting that the varied distribution of CDT in bacteria implicates many human pathogens as possessors of genotoxic activity.