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Genetic Screen for Chromosome Instability in Mice: Mcm4 and Breast Cancer
Naoko Shima, Tavanna R. Buske and John C. Schimenti
volume 6 | issue 10
15 May 2007Pages: 1135 - 1140
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We recently isolated a hypomorphic mutation of Mcm4 in a phenotype-based screen for chromosome instability in mice. This mutation, named Chaos3 (Chromosome aberrations occurring spontaneously 3), causes exclusively mammary adenocarcinomas in ~80% of homozygous females. Mcm4 encodes a subunit of the MCM2-7 complex, the replication-licensing factor and the replicative helicase. The Mcm4Chaos3 mutation appears to destabilize the MCM2-7 complex, causing impaired DNA replication. These findings demonstrate, for the first time, the causative role of an Mcm mutation in cancer development. Furthermore, this raises the possibility that hypomorphic mutations in MCM2-7 genes may increase breast cancer risk in humans.
Authors
Naoko Shima
Tavanna R. Buske
University of Minnesota, Minneapolis, Minnesota
John C. Schimenti
Cornell University, Ithaca, New York
We now provide open access to journal articles published online for one year or more. This article may be downloaded at the following link:
Download PDF If the document does not open, please right-click on the link (control-click on a Macintosh) and select the option to save the file to disk.