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Science. 2010 Aug 20;329(5994):943-6. doi: 10.1126/science.1190966.

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

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1
Department of Molecular Biology and Genetics, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.

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  • Science. 2010 Oct 22;330(6003):448.

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.

Comment in

PMID:
20724634
PMCID:
PMC3700424
DOI:
10.1126/science.1190966
[Indexed for MEDLINE]
Free PMC Article
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