Shima Naoko, Buske Tavanna R, Schimenti John C
Department of Genetics, Cell Biology and Development, Medical School and College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA.
Cell Cycle. 2007 May 15;6(10):1135-40. doi: 10.4161/cc.6.10.4250. Epub 2007 May 5.
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 approximately 80% of homozygous females. Mcm4 encodes a subunit of the MCM2-7 complex, the replication-licensing factor and the replicative helicase. The Mcm4(Chaos3) 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.
我们最近在一项基于表型的小鼠染色体不稳定性筛选中分离出了Mcm4的一个低表达突变。这个名为Chaos3（自发发生染色体畸变3）的突变，在大约80%的纯合雌性小鼠中仅引发乳腺腺癌。Mcm4编码MCM2 - 7复合物的一个亚基，该复合物是复制许可因子和复制解旋酶。Mcm4(Chaos3)突变似乎会使MCM2 - 7复合物不稳定，导致DNA复制受损。这些发现首次证明了Mcm突变在癌症发展中的致病作用。此外，这增加了MCM2 - 7基因低表达突变可能会增加人类患乳腺癌风险的可能性。
