Source:http://linkedlifedata.com/resource/pubmed/id/17143284
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2006-12-28
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| pubmed:abstractText |
Mcm4 (minichromosome maintenance-deficient 4 homolog) encodes a subunit of the MCM2-7 complex (also known as MCM2-MCM7), the replication licensing factor and presumptive replicative helicase. Here, we report that the mouse chromosome instability mutation Chaos3 (chromosome aberrations occurring spontaneously 3), isolated in a forward genetic screen, is a viable allele of Mcm4. Mcm4(Chaos3) encodes a change in an evolutionarily invariant amino acid (F345I), producing an apparently destabilized MCM4. Saccharomyces cerevisiae strains that we engineered to contain a corresponding allele (resulting in an F391I change) showed a classical minichromosome loss phenotype. Whereas homozygosity for a disrupted Mcm4 allele (Mcm4(-)) caused preimplantation lethality, Mcm(Chaos3/-) embryos died late in gestation, indicating that Mcm4(Chaos3) is hypomorphic. Mutant embryonic fibroblasts were highly susceptible to chromosome breaks induced by the DNA replication inhibitor aphidicolin. Most notably, >80% of Mcm4(Chaos3/Chaos3) females succumbed to mammary adenocarcinomas with a mean latency of 12 months. These findings suggest that hypomorphic alleles of the genes encoding the subunits of the MCM2-7 complex may increase breast cancer risk.
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| pubmed:grant | |
| pubmed:commentsCorrections | |
| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
1061-4036
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
39
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
93-8
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| pubmed:dateRevised |
2007-12-3
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| pubmed:meshHeading |
pubmed-meshheading:17143284-Adenocarcinoma,
pubmed-meshheading:17143284-Amino Acid Sequence,
pubmed-meshheading:17143284-Animals,
pubmed-meshheading:17143284-Cells, Cultured,
pubmed-meshheading:17143284-Chromosomal Instability,
pubmed-meshheading:17143284-Chromosome Mapping,
pubmed-meshheading:17143284-DNA Helicases,
pubmed-meshheading:17143284-DNA Mutational Analysis,
pubmed-meshheading:17143284-Female,
pubmed-meshheading:17143284-Fetal Viability,
pubmed-meshheading:17143284-Male,
pubmed-meshheading:17143284-Mammary Neoplasms, Animal,
pubmed-meshheading:17143284-Mice,
pubmed-meshheading:17143284-Mice, Inbred C3H,
pubmed-meshheading:17143284-Mice, Inbred C57BL,
pubmed-meshheading:17143284-Mice, Transgenic,
pubmed-meshheading:17143284-Molecular Sequence Data,
pubmed-meshheading:17143284-Sequence Homology, Amino Acid
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| pubmed:year |
2007
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| pubmed:articleTitle |
A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.
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| pubmed:affiliation |
Department of Genetics, Cell Biology and Development, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA. shima023@umn.edu
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| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, N.I.H., Extramural
|