Abstract
Eukaryotic chromosomal DNA is licensed for replication precisely once in each cell cycle. The mini-chromosome maintenance (MCM) complex plays a role in this replication licensing. We have determined the structure of a fragment of MCM from Methanobacterium thermoautotrophicum (mtMCM), a model system for eukaryotic MCM. The structure reveals a novel dodecameric architecture with a remarkably long central channel. The channel surface has an unusually high positive charge and binds DNA. We also show that the structure of the N-terminal fragment is conserved for all MCMs proteins despite highly divergent sequences, suggesting a common architecture for a similar task: gripping/remodeling DNA and regulating MCM activity. An mtMCM mutant protein equivalent to a yeast MCM5 (CDC46) protein with the bob1 mutation at its N terminus has only subtle structural changes, suggesting a Cdc7-bypass mechanism by Bob1 in yeast. Yeast bypass experiments using MCM5 mutant proteins support the hypothesis for the bypass mechanism.
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Change history
10 February 2003
Corrected HTML, added footnote
Notes
*Note: In the version of this article initially published online, this paper contained two mistakes. The first mistake is in the legend of Fig. 3b; the correct legend should read: "b, Side view of the N-mtMCM dodecamer showing the predominantly negatively charged (red) outer surface". The second mistake is in the first paragraph of page 5 (third line from the top); the correct sentence should read: "A surface charge calculation shows that the inner surface of the entire channel is strongly positive (Fig. 3c); in contrast, the outside surface is mostly negative (Fig. 3b)". This mistake has been corrected in the HTML and print versions of the article.
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Acknowledgements
We thank S. Harrison for comments on the manuscript, L. Pessoa-Brandão, R. Zhao, D. Li, T. Gould and L. Wilson for assistance and other members of the Chen group for comments and input; R. Zhang at 19id in Argonne National Laboratory (APS) and the staff at 14bmc in APS and X25 and X4A in Brookhaven National Laboratory for assistance in data collection; and the UCHSC X-ray center in Biomolecular Structure Program for support. This work is supported by start-up and cancer-center funds from UCHSC to X.C. and an NIH grant to R.S.
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Fletcher, R., Bishop, B., Leon, R. et al. The structure and function of MCM from archaeal M. Thermoautotrophicum. Nat Struct Mol Biol 10, 160–167 (2003). https://doi.org/10.1038/nsb893
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DOI: https://doi.org/10.1038/nsb893
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