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