High impact information on MCM2

• A family of related yeast replication proteins, MCM2, 3 and 5 (also called, after cell-division cycle, CDC46), resemble licensing factor, entering the nucleus only during mitosis [1].
• Cell proliferation and DNA replication defects in a Drosophila MCM2 mutant [2].
• Once inside the nucleus, a fraction of the MCM2 and MCM3 proteins becomes tightly associated with DNA [3].
• We show further that the nuclear and subnuclear localizations of the MCM2 and MCM3 proteins are temporally regulated with respect to the cell cycle [3].
• MCM2 encodes a protein of 890 amino acids containing a putative zinc-finger domain that is essential for Mcm2 function [4].

Biological context of MCM2

• MCM2 and MCM3 are essential genes believed to play important roles in the initiation of DNA replication in Saccharomyces cerevisiae [4].
• These results are consistent with the notion that the N-terminal phosphorylation of MCM2, MCM4, and MCM6 may play functionally redundant but essential roles in initiation of DNA replication [5].
• These include the Saccharomyces cerevisiae MCM2 and MCM3 proteins, which are needed for the efficient function of certain replication origins, and S.cerevisiae CDC46, which is required for the initiation of chromosome replication [6].
• Mutants defective in Mcm2 or Mcm3 are remarkably similar in phenotype [4].
• Identification of Cdc6 protein domains involved in interaction with Mcm2 protein and Cdc4 protein in budding yeast cells [7].

Anatomical context of MCM2

• Disruption of AKAP95-MCM2 interaction with an AKAP95-(1-195) peptide within HeLa cell nuclei abolishes initiation of DNA replication in G1 phase and the elongation phase of replication in vitro without affecting global nuclear organization or import [8].

Associations of MCM2 with chemical compounds

• Interestingly, when all six putative Cdc28 phosphorylation sites in Cdc6p were changed to alanine, a 6-7-fold increase in binding to Mcm2p was observed [7].
• Furthermore, in cells lacking either the DNA damage or the DNA replication checkpoints, the spindle checkpoint contributed to the arrest responses of cells to the DNA-damaging agent methyl methanesulfonate, the replication inhibitor hydroxyurea, and mutations affecting Mcm2p and Orc2p [9].

Physical interactions of MCM2

• Here we show that both Cdc45p and replication protein A (RPA) bind to Mcm2p at the G(1)-S transition in an S-CDK-dependent manner [10].

Other interactions of MCM2

• Furthermore, overproduction of Mcm3 accentuates the deleterious effect of the mcm2-1 mutation, whereas overproduction of Mcm2 partially complements the mcm3-1 mutation [4].
• Class 1 includes genes that encode components of the pre-RC and pre-IC and are represented by SLM3, 4 and 5 which are allelic to MCM7, MCM2 and CDC45, respectively [11].
• Significantly, when pretreated with alkaline phosphatase, Mcm2p became completely inactive as a substrate, suggesting that it must be phosphorylated by other protein kinase(s) to be a substrate for the Cdc7p/Dbf4p complex [12].
• Cdc45p is required for recruiting DNA polymerase alpha onto chromatin, and it associates with Mcm2p, RPA, and DNA polymerase epsilon only during S phase [10].
• We have assayed the kinase activity of endogenous levels of Cdc7p kinase by using a likely physiological target, Mcm2p, as a substrate [13].

Analytical, diagnostic and therapeutic context of MCM2

• Chromatin-immunoprecipitation analysis reveals that similarly to the mitotic cell cycle, Mcm2 binds origins in G1 and meiotic S phases, and at the end of the second meiotic division, it is gradually removed from chromatin [14].
• Immunoblotting results demonstrate that mouse homologues of Mcm2, Mcm5, and Cdc6 are displaced from chromatin in quiescent cells [15].
• Using degenerate primers and low stringency PCR conditions six different DNA sequences were identified with highest sequence similarity to MCM2, 3, 4, 5, 6 and 7 [16].
• RESULTS: To identify essential origin sequences genome-wide, we utilized a tiled oligonucleotide array (NimbleGen) to map the ORC and Mcm2p binding sites at high resolution [17].

References