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The HIV-Tat protein induces chromosome number aberrations by affecting mitosis.

机译:HIV-Tat蛋白通过影响有丝分裂诱导染色体数目畸变。

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To analyze the effects of the HIV-Tat-tubulin interaction, we microinjected HIV-Tat purified protein into Drosophila syncytial embryos. Following the Tat injection, altered timing of the cortical nuclear cycles was observed; specifically, the period between the nuclear envelope breakdown and anaphase initiation was lengthened as was the period between anaphase initiation and the formation of the next nuclear envelope. These two periods correspond to kinetochore alignment at metaphase and to mitosis exit, respectively. We also demonstrated that these two delays are the consequence of damage specifically induced by Tat on kinetochore alignment and on the timing of sister chromatid segregation at anaphase. Furthermore, we show that the expression of Tat in Drosophila larvae brain cells produces a significant percentage of polyploid and aneuploid cells. The results reported here indicate that Tat impairs the mitotic process and that Tat-tubulin interaction appears to be responsible for the observed defects. The presence of polyploid and aneuploid cells is consistent with a delay or arrest in the M phase of a substantial fraction of the cells expressing Tat, suggesting that mitotic spindle checkpoints are overridden following Tat expression.
机译:为了分析HIV-Tat-微管蛋白相互作用的影响,我们将HIV-Tat纯化的蛋白显微注射到果蝇合胞体胚胎中。 Tat注射后,观察到皮质核循环的时间发生了改变;具体而言,延长了核被膜破裂和后期开始之间的时间,以及后期开始和下一个核被膜形成之间的时间。这两个时期分别对应中期的线粒体排列和有丝分裂出口。我们还证明了这两个延迟是Tat对线粒体排列和后期染色单体分离的特定时间造成的损伤的结果。此外,我们表明,在果蝇幼虫脑细胞中Tat的表达产生大量的多倍体和非整倍体细胞。此处报道的结果表明,Tat损害有丝分裂过程,而Tat-微管蛋白相互作用似乎是所观察到的缺陷的原因。多倍体和非整倍体细胞的存在与大部分表达Tat的细胞在M期中的延迟或停滞相一致,表明在Tat表达后有丝分裂纺锤体检查点被覆盖。

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