A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Research Abstract Details 

Research Abstract Table of Contents

Jump to the:

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Abstract Text:

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.

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Publishing Authors By Initials

For similar biochemical phenomena, metabolism, and nutrition: biochemical phenomena: sequence homology: sequence homology, amino acid research abstracts see: biochemical phenomena, metabolism, and nutrition: biochemical phenomena: sequence homology: sequence homology, amino acid research

PUBMED ID PMID:

MEDLINE DATE:

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Nature genetics

VOLUME: 39

Page Numbers: 93-8

Journal Abbreviation: Nat. Genet.

ISSN: 1061-4036

DAY: 3

MONTH: 12

YEAR: 2006

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 9216904

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Keywords Mesh Terms:

KEYWORDS: Sequence Homology, Amino Acid

MESH TERMS: genetics

Chemical & Substance for Abstract: A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Information

Substance Name: MCM4 protein, mouse

Registry Number: EC 3.6.1.-

Grant and Affiliation Information for A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.

AFFILIATION: Department of Genetics, Cell Biology and Development, College of Biological Sciences, University of Minnesota, Minneapolis, Minnesota 55455, USA. shima023@umn.edu

Country: United States

AGENCY: United States NIGMS

GRANT: R01 GM45415

ACRONYM: GM

MEDLINETA: Nat Genet

REFSOURCE: Nat Genet. 2007 Jan;39(1):10-1

DATABASENAME:

ACCESSION NUMBER:

Number Hits: 0

A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice Related Publications

• A dominant, recombination-defective allele of Dmc1 causing male-specific sterility.
• A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice.
• An allelic series uncovers novel roles of the BRCT domain-containing protein PTIP in mouse embryonic vascular development.
• Different regulatory systems operate in the midpiece and principal piece of the mammalian sperm flagellum.
• Fast forward to new genes in mammalian reproduction.
• Genetic screen for chromosome instability in mice: Mcm4 and breast cancer.
• Mouse pachytene checkpoint 2 (trip13) is required for completing meiotic recombination but not synapsis.
• Mutation in mouse hei10, an e3 ubiquitin ligase, disrupts meiotic crossing over.
• ORFless, intronless, and mutant transcription units in the mouse t complex responder (Tcr) locus.
• Sperm motility defects and infertility in male mice with a mutation in Nsun7, a member of the Sun domain-containing family of putative RNA methyltransferases.
• The dual bromodomain and WD repeat-containing mouse protein BRWD1 is required for normal spermiogenesis and the oocyte-embryo transition.
• The mouse gcd2 mutation causes primordial germ cell depletion.