Loss of DNA replication control is a potent inducer of gene amplification.

Loss of DNA replication control is a potent inducer of gene amplification.
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DNA复制控制的丧失是基因扩增的有效诱导剂。

DOI:
10.1126/science.1190966
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发表时间:
2010-08-20
期刊:
Science (New York, N.Y.)
影响因子:
--
通讯作者:
Li JJ
Li JJ
中科院分区:
其他
文献类型:
--
作者:
Green BM;Finn KJ;Li JJ

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真核细胞使用许多机制来确保它们的DNA没有片段被不适当地重新复制,但是这种对基因组稳定性的严格控制的重要性还没有被测试。在这里,我们表明,在酿酒酵母中的再复制可以强烈诱导基因扩增的初始步骤,增加基因拷贝数从一个到两个或更多。所得到的扩增子由大的内部染色体区段组成,所述染色体区段由Ty重复元件限定,并且在其内源性基因座处以直接的头对尾方向在染色体内排列。这些再复制诱导的基因扩增由重复元件之间的非等位基因同源重组介导。我们认为重新复制可能是基因拷贝数变化的一个因素,这在癌症生物学、进化和人类遗传学等领域很重要。
Eukaryotic cells use numerous mechanisms to ensure that no segment of their DNA is inappropriately re-replicated, but the importance of this stringent control on genome stability has not been tested. Here we show that re-replication in Saccharomyces cerevisiae can strongly induce the initial step of gene amplification, increasing gene copy number from one to two or more. The resulting amplicons consist of large internal chromosomal segments that are bounded by Ty repetitive elements and are intrachromosomally arrayed at their endogenous locus in direct head-to-tail orientation. These re-replication–induced gene amplifications are mediated by nonallelic homologous recombination between the repetitive elements. We suggest that re-replication may be a contributor to gene copy number changes, which are important in fields such as cancer biology, evolution, and human genetics.
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发表时间: 2007-12-24
影响因子: 15.3
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