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Gene Review

Mcm4  -  minichromosome maintenance deficient 4...

Mus musculus

Synonyms: 19G, AI325074, AU045576, CDC21 homolog, Cdc21, ...
 
 
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Disease relevance of Mcm4

  • Challenging this notion, a new study in mice shows that a hypomorphic mutation in the gene encoding the replication initiation factor Mcm4 leads to genetic instability and predisposes to mammary adenocarcinomas [1].
  • MATERIALS AND METHODS: Human pancreatic cancer xenografts (PZX-40/19G) were treated s.c. with 10 mg/kg b.w. SILA-409 every second day for 34 days [2].
 

High impact information on Mcm4

  • In contrast, the Mcm4/6/7 complex containing a zinc finger mutant of Mcm4 with partially impaired DNA binding activity exhibited elevated DNA helicase activity [3].
  • Mutations of consensus CDK sites in Mcm4p and Mcm7p also have no phenotypic consequences [4].
  • Comparative analyses of the genome strongly suggested that the region contains only two genes for Prkdc and Mcm4; however, several conserved sequences and cis elements were also predicted [5].
  • We previously reported that helicase and ATPase activities of the mammalian Mcm4/6/7 complex are activated specifically by thymine-rich single-stranded DNA [6].
  • Strand displacement by Mcm4/6/7 is inhibited, as the GC content of the duplex region increases [6].
 

Associations of Mcm4 with chemical compounds

  • Loss of thymine residues from one single-strand results in significant decrease of unwinding efficacy, suggesting that concurrent bidirectional unwinding by a single double hexameric Mcm4/6/7 may play a role in efficient unwinding of the bubble [6].
 

Analytical, diagnostic and therapeutic context of Mcm4

  • Molecular cloning of cDNA encoding mouse Cdc21 and CDC46 homologs and characterization of the products: physical interaction between P1(MCM3) and CDC46 proteins [7].

References

  1. Chaotic license for genetic instability and cancer. Dutta, A. Nat. Genet. (2007) [Pubmed]
  2. Effect of SILA-409, a new organosilicon multidrug resistance modifier, on human pancreatic cancer xenografts. Zalatnai, A., Molnár, J. In Vivo (2006) [Pubmed]
  3. Roles of Mcm7 and Mcm4 subunits in the DNA helicase activity of the mouse Mcm4/6/7 complex. You, Z., Ishimi, Y., Masai, H., Hanaoka, F. J. Biol. Chem. (2002) [Pubmed]
  4. Different phenotypes in vivo are associated with ATPase motif mutations in Schizosaccharomyces pombe minichromosome maintenance proteins. Gómez, E.B., Catlett, M.G., Forsburg, S.L. Genetics (2002) [Pubmed]
  5. Sequence analysis of 193.4 and 83.9 kbp of mouse and chicken genomic DNAs containing the entire Prkdc (DNA-PKcs) gene. Fujimori, A., Hashimoto, H., Araki, R., Saito, T., Sato, S., Kasama, Y., Tsutsumi, Y., Mori, M., Fukumura, R., Ohhata, T., Tatsumi, K., Abe, M. Radiat. Res. (2002) [Pubmed]
  6. DNA binding and helicase actions of mouse MCM4/6/7 helicase. You, Z., Masai, H. Nucleic Acids Res. (2005) [Pubmed]
  7. Molecular cloning of cDNA encoding mouse Cdc21 and CDC46 homologs and characterization of the products: physical interaction between P1(MCM3) and CDC46 proteins. Kimura, H., Takizawa, N., Nozaki, N., Sugimoto, K. Nucleic Acids Res. (1995) [Pubmed]
 
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