Journal
SCIENCE
Volume 329, Issue 5994, Pages 943-946Publisher
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/science.1190966
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Funding
- Sandler Program in Basic Sciences
- Stewart Trust
- UCSF Research Evaluation and Allocation Committee
- UCSF Academic Senate
- UC Cancer Research Coordinating Committee
- NIH [R01 GM59704]
- NSF
- Department of Defense [W81XWH-04-1-0409]
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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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