Genetic screen for chromosome instability in mice: Mcm4 and breast cancer.
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.
Shima
Naoko
N
Department of Genetics, Cell Biology and Development, Medical School and College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA. shima023@umn.edu
Buske
Tavanna R
TR
Schimenti
John C
JC
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics*; D043171:Chromosomal Instability / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005820:Genetic Testing; D051379:Mice; D015162:Micronucleus Tests; D064148:Minichromosome Maintenance Complex Component 4; D009154:Mutation / Q000235:genetics
D004265:DNA Helicases; C516793:Mcm4 protein, mouse; D064148:Minichromosome Maintenance Complex Component 4