High impact information on MCM3

• Identification of the yeast MCM3-related protein as a component of Xenopus DNA replication licensing factor [1].
• Once inside the nucleus, a fraction of the MCM2 and MCM3 proteins becomes tightly associated with DNA [2].
• We show further that the nuclear and subnuclear localizations of the MCM2 and MCM3 proteins are temporally regulated with respect to the cell cycle [2].
• Here, we show that Cdc47p assembles into stable complexes with two other members of the MCM family, Cdc46p and Mcm3p [3].
• MCM3 is an essential gene involved in the maintenance of minichromosomes in yeast cells [4].

Biological context of MCM3

• MCM2 and MCM3 are essential genes believed to play important roles in the initiation of DNA replication in Saccharomyces cerevisiae [5].
• Mutants defective in Mcm2 or Mcm3 are remarkably similar in phenotype [5].
• Two mcm3 mutations affect different steps in the initiation of DNA replication [6].
• Mcm3-10 contains a P118L substitution that compromises its interaction with Mcm5 and the recruitment of Mcm3 and Mcm7 to a replication origin [6].
• Two types of antibodies were prepared: one directed against an oligopeptide specific to P1 protein, a mammalian homologue of yeast MCM3, and the other against an oligopeptide with a DEAD box motif, which is a highly conserved sequence in the P1 protein family [7].

Anatomical context of MCM3

• The first requires the entry of a cytosolic 'loading factor' that is excluded by the nuclear membrane; subsequently, MCM3 can bind to chromatin in the presence or absence of a nuclear membrane, but only if the loading factor has gained access in the absence of the membrane [8].
• BACKGROUND: GANP, carrying DNA-primase and MCM3-binding domains, is up-regulated in germinal centre B cells [9].

Associations of MCM3 with chemical compounds

• Study of the Mcm3/7p ATPase shows that an essential arginine in Mcm3p is required for hydrolysis of the ATP bound to Mcm7p [10].

Other interactions of MCM3

• Furthermore, overproduction of Mcm3 accentuates the deleterious effect of the mcm2-1 mutation, whereas overproduction of Mcm2 partially complements the mcm3-1 mutation [5].
• CDC45 also interacts genetically with ORC2, the gene encoding the second subunit of the origin recognition complex, ORC, and MCM3, another member of the MCM family [11].
• We also identify a Crm1-dependent nuclear export signal (NES) adjacent to the Mcm3 NLS [12].
• The mad2Delta mutation partially relieved the arrest responses of cells to mutations affecting the replication proteins Mcm3p and Pol1p [13].

Analytical, diagnostic and therapeutic context of MCM3

• Sequence analysis of full length cDNA clones corresponding to the MCM3, 6 and 7 fragment proves the existence of six MCM genes in Drosophila melanogaster [14].

References