Genomic instability driven by the human T-cell leukemia virus type I (HTLV-1) oncoprotein, Tax
Genomic instability driven by the human T-cell leukemia virus type I (HTLV-1) oncoprotein, Tax
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DOI：
10.1038/sj.onc.1205898
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发表时间：
2002-10-17
期刊：
影响因子：
8
通讯作者：
Marriott, SJ
中科院分区：
文献类型：
--
作者：
Lemoine, FJ;Marriott, SJ
保持基因组稳定性的重要性由转化细胞通常含有多种染色体异常例如整倍性、易位和倒位的事实证明。基因扩增是基因组不稳定性的一个充分表征的标志，被认为是由双链染色体断裂形成后的重组事件引起的。因此，基因扩增频率作为基因组稳定性的指标。PALA检测旨在直接测量特定基因CAD在细胞基因组内扩增的频率。我们已经使用PALA测定来分析人类T细胞白血病病毒I型（HTLV-1）癌蛋白Tax对基因组扩增的影响。我们证明，表达Tax的细胞比对照细胞进行基因扩增的可能性高5倍。此外，我们表明，税收改变了细胞的能力，进行典型的PAA介导的G，期细胞周期停滞，从而使细胞复制DNA在适当的核苷酸池的情况下。这种效应可能是Tax诱导基因扩增的机制。这些数据表明，HTLV-1 Tax改变了细胞的基因组稳定性，这种作用可能在Tax介导的HTLV-1相关细胞转化中发挥重要作用。
The importance of maintaining genomic stability is evidenced by the fact that transformed cells often contain a variety of chromosomal abnormalities such as euploidy, translocations, and inversions. Gene amplification is a well-characterized hallmark of genomic instability thought to result from recombination events following the formation of double-strand, chromosomal breaks. Therefore, gene amplification frequency serves as an indicator of genomic stability. The PALA assay is designed to measure directly the frequency with which a specific gene, CAD, is amplified within a cell's genome. We have used the PALA assay to analyse the effects of the human T-cell leukemia virus type I (HTLV-1) oncoprotein, Tax, on genomic amplification. We demonstrate that Tax-expressing cells are five-times more likely to undergo gene amplification than control cells. Additionally, we show that Tax alters the ability of cells to undergo the typical PALA-mediated G, phase cell cycle arrest, thereby allowing cells to replicate DNA in the absence of appropriate nucleotide pools. This effect is likely the mechanism by which Tax induces gene amplification. These data suggest that HTLV-1 Tax alters the genomic stability of cells, an effect that may play an important role in Tax-mediated, HTLV-1 associated cellular transformation.