Replication Error Amplified

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Science  20 Aug 2010:
Vol. 329, Issue 5994, pp. 911-913
DOI: 10.1126/science.1194261

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Cells have a seemingly endless array of regulators to provide for fast and accurate DNA replication. Most cells succeed in doing it right, each and every time they divide, which is testimony to the powers of evolution. Failure to limit DNA replication to just once every cell cycle can lead to genome rearrangements, in particular to “amplification,” or an increase in the number of copies of some genes. Amplification can drive abnormal cell growth, and cancer cells often have amplified oncogenes (1). How gene amplification occurs, however, is unclear. One mechanism involves the breaking and fusion of aberrant chromosomes, a process first discovered by Nobel Laureate Barbara McClintock in the 1950s (2), which leads to extra copies of genes that are joined together (3). Another proposed mechanism involves defects in the “re-replication” controls that shut down the DNA-copying process after a single duplication, but this idea had not been testable (4). On page 943 of this issue, Green et al. overcome that hurdle with an extravagant experimental system in budding yeast that demonstrates that re-replication is indeed a potent mechanism of gene amplification (5).