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A new process for activation of the replicative helicase in the initiation of DNA replication
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| Current Biology (Advance Online Publication) | ||
| Kanemaki Laboratory, Molecular Function Laboratory | ||
| Mcm10 plays a role in functioning of the eukaryotic replicative DNA helicase, Cdc45-Mcm-GINS George Watase, Haruhiko Takisawa and Masato T. Kanemaki Current Biology Published online: January 26, 2012. http://dx.doi.org/10.1016/j.cub.2012.01.023 Human body is said to be composed of 60 trillions of cells, all of which are derived from one fertilized egg. For cell proliferation, chromosomal DNA, that contains genes, has to be accurately duplicated before the distribution to two daughter cells. If there was a problem in this process, it might cause cell death or carcinogenesis. Therefore, it is important to understand the molecular mechanism of DNA replication. DNA replication is controlled and initiated by a sequential assembly of replication proteins that are evolutionarily conserved from yeast to humans. Recent studies revealed that activation of the Mcm2-7 DNA helicase is a key step for the initiation. Mcm2-7 is inactive as it own, but is activated as the CMG (Cdc45-Mcm-GINS) complex by the association of two additional factors, Cdc45 and GINS, in S phase. In this study, we revealed that the Mcm10 replication protein functions after CMG formation and is required for origin unwinding. Our study indicates that CMG formation is not sufficient for the activation of the helicase. We observed budding yeast cells depleted of Mcm10 to see the phenotype in this study. Protein depletion was done by using the auxin-inducible degron (AID) method, that was developed in our laboratory. The details of the AID method can be found in this website. http://www.nig.ac.jp/labs/MolFunc/Molecular_Function_HP/What_is_AID.html
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