失去 DNA 复制控制是基因扩增的有力诱导剂。
Loss of DNA replication control is a potent inducer of gene amplification.
机构信息
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
出版信息
Science. 2010 Aug 20;329(5994):943-6. doi: 10.1126/science.1190966.
Abstract
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.
摘要
真核细胞使用多种机制来确保其 DNA 没有不适当的重复复制，但这种对基因组稳定性的严格控制的重要性尚未得到验证。在这里，我们表明酿酒酵母中的重复复制可以强烈诱导基因扩增的初始步骤，将基因拷贝数从一个增加到两个或更多。由此产生的扩增子由 Ty 重复元件包围的大型内部染色体片段组成，并以直接头对头的方向在其内源位置处在染色体内排列。这些重复复制诱导的基因扩增是由重复元件之间的非等位基因同源重组介导的。我们认为，重复复制可能是导致基因拷贝数变化的原因之一，而基因拷贝数变化在癌症生物学、进化和人类遗传学等领域非常重要。
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1
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Nat Rev Genet. 2010 Feb;11(2):97-108. doi: 10.1038/nrg2689. Epub 2010 Jan 6.
2
Copy number variation in human health, disease, and evolution.人类健康、疾病与进化中的拷贝数变异
Annu Rev Genomics Hum Genet. 2009;10:451-81. doi: 10.1146/annurev.genom.9.081307.164217.
3
Mechanisms of change in gene copy number.基因拷贝数变化的机制。
Nat Rev Genet. 2009 Aug;10(8):551-64. doi: 10.1038/nrg2593.
4
A prominent role for segmental duplications in modeling eukaryotic genomes.片段重复在真核生物基因组建模中的重要作用。
C R Biol. 2009 Feb-Mar;332(2-3):254-66. doi: 10.1016/j.crvi.2008.07.005. Epub 2008 Dec 2.
5
Segmental duplications arise from Pol32-dependent repair of broken forks through two alternative replication-based mechanisms.节段性重复通过两种基于复制的替代机制，由依赖Pol32的断裂叉修复产生。
PLoS Genet. 2008 Sep 5;4(9):e1000175. doi: 10.1371/journal.pgen.1000175.
6
Replication licensing and cancer--a fatal entanglement?复制许可与癌症——致命的纠缠？
Nat Rev Cancer. 2008 Oct;8(10):799-806. doi: 10.1038/nrc2500. Epub 2008 Aug 29.
7
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8
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