High impact information on MCM10

• Localization of human Mcm10 is spatially and temporally regulated during the S phase [1].
• In the late S and G phases, GFP-Mcm10 was localized to nucleoli [1].
• To study the localization dynamics of human Mcm10, we established HeLa cell lines expressing green fluorescent protein (GFP)-tagged Mcm10 [1].
• Recently, we identified a human Mcm10 homolog and found that it is regulated by proteolysis and phosphorylation in a cell cycle-dependent manner and that it binds chromatin exclusively during the S phase of the cell cycle [1].
• Drosophila MCM10 interacts with members of the prereplication complex and is required for proper chromosome condensation [2].

Biological context of MCM10

• Expression of MCM10 and TopBP1 is regulated by cell proliferation and UV irradiation via the E2F transcription factor [3].
• The CENP-B homolog, Abp1, interacts with the initiation protein Cdc23 (MCM10) and is required for efficient DNA replication in fission yeast [4].
• Here we show that Abp1 interacts with the DNA replication protein Cdc23 (MCM10) in a two-hybrid assay, and that the Deltaabp1 mutant displays a synthetic phenotype with a cdc23 temperature-sensitive mutant [4].
• This observation prompted us to look more directly at the effect of MCM10 mutations on the expression of a reporter gene in the mating type locus and to assay for physical interactions between Mcm10 and known silencing factors [5].
• A novel zinc finger is required for Mcm10 homocomplex assembly [6].

Associations of MCM10 with chemical compounds

• We showed, by performing chromatin immunoprecipitation that, in response to UV irradiation but not doxorubicin treatment, E2F4 accumulated on the MCM10 and TopBP1 promoters [3].

Physical interactions of MCM10

• These findings, together with data for DNA and p180 binding to an Mcm10 construct that contains both the ID and CTD, provide the first mechanistic insight into how Mcm10 might use a handoff mechanism to load and stabilize pol alpha within the replication fork [7].

Other interactions of MCM10

• The promoter activities of human MCM10 and TopBP1 were demonstrated to be growth dependent via the E2F-responsive sequence [3].
• In this study, we showed that the transcription of human MCM10 and TopBP1 is activated by transcription factors E2F1-3, but not by factors E2F4-7 [3].
• Although (2)the distributions of GFP-Mcm10 during the S phase resembled those of replication foci, GFP-Mcm10 foci did not colocalize with sites of DNA synthesis in most cases [1].
• Nuclear distribution and chromatin association of DNA polymerase alpha-primase is affected by TEV protease cleavage of Cdc23 (Mcm10) in fission yeast [8].

References