| Structural highlights
Function
[MCM7_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.[1] [2] [MCM5_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity.[3] [4] [MCM2_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity; specifically the MCM2-MCM5 association is proposed to be reversible and to mediate a open ring conformation which may facilitate DNA loading. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.[5] [6] [MCM4_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for S phase execution.[7] [8] [MCM3_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Necessary for cell growth.[9] [10] [MCM6_YEAST] Acts as component of the MCM2-7 complex (MCM complex) which is the putative replicative helicase essential for 'once per cell cycle' DNA replication initiation and elongation in eukaryotic cells. The active ATPase sites in the MCM2-7 ring are formed through the interaction surfaces of two neighboring subunits such that a critical structure of a conserved arginine finger motif is provided in trans relative to the ATP-binding site of the Walker A box of the adjacent subunit. The six ATPase active sites, however, are likely to contribute differentially to the complex helicase activity. Once loaded onto DNA, double hexamers can slide on dsDNA in the absence of ATPase activity. Required for the entry in S phase and for cell division.[11] [12]
Publication Abstract from PubMed
DNA replication in eukaryotes is strictly regulated by several mechanisms. A central step in this replication is the assembly of the heterohexameric minichromosome maintenance (MCM2-7) helicase complex at replication origins during G1 phase as an inactive double hexamer. Here, using cryo-electron microscopy, we report a near-atomic structure of the MCM2-7 double hexamer purified from yeast G1 chromatin. Our structure shows that two single hexamers, arranged in a tilted and twisted fashion through interdigitated amino-terminal domain interactions, form a kinked central channel. Four constricted rings consisting of conserved interior beta-hairpins from the two single hexamers create a narrow passageway that tightly fits duplex DNA. This narrow passageway, reinforced by the offset of the two single hexamers at the double hexamer interface, is flanked by two pairs of gate-forming subunits, MCM2 and MCM5. These unusual features of the twisted and tilted single hexamers suggest a concerted mechanism for the melting of origin DNA that requires structural deformation of the intervening DNA.
Structure of the eukaryotic MCM complex at 3.8 A.,Li N, Zhai Y, Zhang Y, Li W, Yang M, Lei J, Tye BK, Gao N Nature. 2015 Aug 13;524(7564):186-91. doi: 10.1038/nature14685. Epub 2015 Jul 29. PMID:26222030[13]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Remus D, Beuron F, Tolun G, Griffith JD, Morris EP, Diffley JF. Concerted loading of Mcm2-7 double hexamers around DNA during DNA replication origin licensing. Cell. 2009 Nov 13;139(4):719-30. doi: 10.1016/j.cell.2009.10.015. Epub 2009 Nov, 5. PMID:19896182 doi:http://dx.doi.org/10.1016/j.cell.2009.10.015
- ↑ Evrin C, Clarke P, Zech J, Lurz R, Sun J, Uhle S, Li H, Stillman B, Speck C. A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc Natl Acad Sci U S A. 2009 Dec 1;106(48):20240-5. doi:, 10.1073/pnas.0911500106. Epub 2009 Nov 12. PMID:19910535 doi:http://dx.doi.org/10.1073/pnas.0911500106
- ↑ Li N, Zhai Y, Zhang Y, Li W, Yang M, Lei J, Tye BK, Gao N. Structure of the eukaryotic MCM complex at 3.8 A. Nature. 2015 Aug 13;524(7564):186-91. doi: 10.1038/nature14685. Epub 2015 Jul 29. PMID:26222030 doi:http://dx.doi.org/10.1038/nature14685
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