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 β-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.
Your institute does not have access to this article
Open Access articles citing this article.
The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer
Nature Communications Open Access 25 May 2022
Nature Open Access 18 May 2022
Nature Communications Open Access 16 March 2022
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Tax calculation will be finalised during checkout.
Get time limited or full article access on ReadCube.
All prices are NET prices.
Electron Microscopy Data Bank
Protein Data Bank
The cryo-EM density map has been deposited in the Electron Microscopy Data Bank (EMDB) under accession number EMD-6338; and the atomic model has been deposited in the Protein Data Bank (PDB) under accession number 3JA8.
O’Donnell, M., Langston, L. & Stillman, B. Principles and concepts of DNA replication in bacteria, archaea, and eukarya. Cold Spring Harb. Perspect. Biol. 5, a010108 (2013)
Costa, A., Hood, I. V. & Berger, J. M. Mechanisms for initiating cellular DNA replication. Annu. Rev. Biochem. 82, 25–54 (2013)
Duderstadt, K. E. & Berger, J. M. A structural framework for replication origin opening by AAA+ initiation factors. Curr. Opin. Struct. Biol. 23, 144–153 (2013)
Tye, B. K. MCM proteins in DNA replication. Annu. Rev. Biochem. 68, 649–686 (1999)
Remus, D. et al. Concerted loading of Mcm2–7 double hexamers around DNA during DNA replication origin licensing. Cell 139, 719–730 (2009)
Evrin, C. et al. A double-hexameric MCM2–7 complex is loaded onto origin DNA during licensing of eukaryotic DNA replication. Proc. Natl Acad. Sci. USA 106, 20240–20245 (2009)
Siddiqui, K., On, K. F. & Diffley, J. F. Regulating DNA replication in eukarya. Cold Spring Harb. Perspect. Biol. 5, a012930 (2013)
Heller, R. C. et al. Eukaryotic origin-dependent DNA replication in vitro reveals sequential action of DDK and S-CDK kinases. Cell 146, 80–91 (2011)
Yeeles, J. T., Deegan, T. D., Janska, A., Early, A. & Diffley, J. F. Regulated eukaryotic DNA replication origin firing with purified proteins. Nature 519, 431–435 (2015)
Tanaka, S. & Araki, H. Helicase activation and establishment of replication forks at chromosomal origins of replication. Cold Spring Harb. Perspect. Biol. 5, a01037 (2013)
Tognetti, S., Riera, A. & Speck, C. Switch on the engine: how the eukaryotic replicative helicase MCM2–7 becomes activated. Chromosoma 124, 13–26 (2015)
Ilves, I., Petojevic, T., Pesavento, J. J. & Botchan, M. R. Activation of the MCM2–7 helicase by association with Cdc45 and GINS proteins. Mol. Cell 37, 247–258 (2010)
Fu, Y. V. et al. Selective bypass of a lagging strand roadblock by the eukaryotic replicative DNA helicase. Cell 146, 931–941 (2011)
Rothenberg, E., Trakselis, M. A., Bell, S. D. & Ha, T. MCM forked substrate specificity involves dynamic interaction with the 5′-tail. J. Biol. Chem. 282, 34229–34234 (2007)
McGeoch, A. T., Trakselis, M. A., Laskey, R. A. & Bell, S. D. Organization of the archaeal MCM complex on DNA and implications for the helicase mechanism. Nature Struct. Mol. Biol. 12, 756–762 (2005)
Costa, A. et al. DNA binding polarity, dimerization, and ATPase ring remodeling in the CMG helicase of the eukaryotic replisome. eLife 3, e03273 (2014)
Graham, B. W., Schauer, G. D., Leuba, S. H. & Trakselis, M. A. Steric exclusion and wrapping of the excluded DNA strand occurs along discrete external binding paths during MCM helicase unwinding. Nucleic Acids Res. 39, 6585–6595 (2011)
Sun, J. et al. Structural and mechanistic insights into Mcm2–7 double-hexamer assembly and function. Genes Dev. 28, 2291–2303 (2014)
Samel, S. A. et al. A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2–7 onto DNA. Genes Dev. 28, 1653–1666 (2014)
Sun, J. et al. Cryo-EM structure of a helicase loading intermediate containing ORC-Cdc6-Cdt1–MCM2–7 bound to DNA. Nature Struct. Mol. Biol. 20, 944–951 (2013)
Costa, A. et al. The structural basis for MCM2–7 helicase activation by GINS and Cdc45. Nature Struct. Mol. Biol. 18, 471–477 (2011)
Hesketh, E. L. et al. DNA induces conformational changes in a recombinant human minichromosome maintenance complex. J. Biol. Chem. 290, 7973–7979 (2015)
Brewster, A. S. et al. Crystal structure of a near-full-length archaeal MCM: functional insights for an AAA+ hexameric helicase. Proc. Natl Acad. Sci. USA 105, 20191–20196 (2008)
Bae, B. et al. Insights into the architecture of the replicative helicase from the structure of an archaeal MCM homolog. Structure 17, 211–222 (2009)
Slaymaker, I. M. et al. Mini-chromosome maintenance complexes form a filament to remodel DNA structure and topology. Nucleic Acids Res. 41, 3446–3456 (2013)
Fletcher, R. J. et al. The structure and function of MCM from archaeal M. thermoautotrophicum . Nature Struct. Biol. 10, 160–167 (2003)
Froelich, C. A., Kang, S., Epling, L. B., Bell, S. P. & Enemark, E. J. A conserved MCM single-stranded DNA binding element is essential for replication initiation. eLife 3, e01993 (2014)
Fu, Y., Slaymaker, I. M., Wang, J., Wang, G. & Chen, X. S. The 1.8-Å crystal structure of the N-terminal domain of an archaeal MCM as a right-handed filament. J. Mol. Biol. 426, 1512–1523 (2014)
Liu, W., Pucci, B., Rossi, M., Pisani, F. M. & Ladenstein, R. Structural analysis of the Sulfolobus solfataricus MCM protein N-terminal domain. Nucleic Acids Res. 36, 3235–3243 (2008)
Miller, J. M., Arachea, B. T., Epling, L. B. & Enemark, E. J. Analysis of the crystal structure of an active MCM hexamer. eLife 3, e03433 (2014)
Cuesta, I. et al. Conformational rearrangements of SV40 large T antigen during early replication events. J. Mol. Biol. 397, 1276–1286 (2010)
Vijayraghavan, S. & Schwacha, A. The eukaryotic Mcm2–7 replicative helicase. Subcell. Biochem. 62, 113–134 (2012)
Bochman, M. L., Bell, S. P. & Schwacha, A. Subunit organization of Mcm2–7 and the unequal role of active sites in ATP hydrolysis and viability. Mol. Cell. Biol. 28, 5865–5873 (2008)
Evrin, C. et al. The ORC/Cdc6/MCM2–7 complex facilitates MCM2–7 dimerization during prereplicative complex formation. Nucleic Acids Res. 42, 2257–2269 (2014)
Slaymaker, I. M. & Chen, X. S. MCM structure and mechanics: what we have learned from archaeal MCM. Subcell. Biochem. 62, 89–111 (2012)
Bochman, M. L. & Schwacha, A. The Mcm complex: unwinding the mechanism of a replicative helicase. Microbiol. Mol. Biol. Rev. 73, 652–683 (2009)
Shima, N. et al. A viable allele of Mcm4 causes chromosome instability and mammary adenocarcinomas in mice. Nature Genet. 39, 93–98 (2007)
Hardy, C. F., Dryga, O., Seematter, S., Pahl, P. M. & Sclafani, R. A. mcm5/cdc46-bob1 bypasses the requirement for the S phase activator Cdc7p. Proc. Natl Acad. Sci. USA 94, 3151–3155 (1997)
Bleichert, F., Botchan, M. R. & Berger, J. M. Crystal structure of the eukaryotic origin recognition complex. Nature 519, 321–326 (2015)
Enemark, E. J. & Joshua-Tor, L. Mechanism of DNA translocation in a replicative hexameric helicase. Nature 442, 270–275 (2006)
Kang, S., Warner, M. D. & Bell, S. P. Multiple functions for Mcm2–7 ATPase motifs during replication initiation. Mol. Cell 55, 655–665 (2014)
Coster, G., Frigola, J., Beuron, F., Morris, E. P. & Diffley, J. F. Origin licensing requires ATP binding and hydrolysis by the MCM replicative helicase. Mol. Cell 55, 666–677 (2014)
Bell, S. D. & Botchan, M. R. The minichromosome maintenance replicative helicase. Cold Spring Harb. Perspect. Biol. 5, a012807 (2013)
Jenkinson, E. R. & Chong, J. P. Minichromosome maintenance helicase activity is controlled by N- and C-terminal motifs and requires the ATPase domain helix-2 insert. Proc. Natl Acad. Sci. USA 103, 7613–7618 (2006)
Gai, D., Zhao, R., Li, D., Finkielstein, C. V. & Chen, X. S. Mechanisms of conformational change for a replicative hexameric helicase of SV40 large tumor antigen. Cell 119, 47–60 (2004)
On, K. F. et al. Prereplicative complexes assembled in vitro support origin-dependent and independent DNA replication. EMBO J. 33, 605–620 (2014)
Bruck, I. & Kaplan, D. L. The Dbf4-Cdc7 kinase promotes Mcm2–7 ring opening to allow for single-stranded DNA extrusion and helicase assembly. J. Biol. Chem. 290, 1210–1221 (2015)
Bruck, I. & Kaplan, D. L. Cdc45 protein-single-stranded DNA interaction is important for stalling the helicase during replication stress. J. Biol. Chem. 288, 7550–7563 (2013)
Fien, K. et al. Primer utilization by DNA polymerase α-primase is influenced by its interaction with Mcm10p. J. Biol. Chem. 279, 16144–16153 (2004)
Eisenberg, S., Korza, G., Carson, J., Liachko, I. & Tye, B. K. Novel DNA binding properties of the Mcm10 protein from Saccharomyces cerevisiae . J. Biol. Chem. 284, 25412–25420 (2009)
Janke, C. et al. A versatile toolbox for PCR-based tagging of yeast genes: new fluorescent proteins, more markers and promoter substitution cassettes. Yeast 21, 947–962 (2004)
Zhai, Y., Yung, P. Y., Huo, L. & Liang, C. Cdc14p resets the competency of replication licensing by dephosphorylating multiple initiation proteins during mitotic exit in budding yeast. J. Cell Sci. 123, 3933–3943 (2010)
Scheres, S. H. A Bayesian view on cryo-EM structure determination. J. Mol. Biol. 415, 406–418 (2012)
Li, X. et al. Electron counting and beam-induced motion correction enable near-atomic-resolution single-particle cryo-EM. Nature Methods 10, 584–590 (2013)
Shaikh, T. R. et al. SPIDER image processing for single-particle reconstruction of biological macromolecules from electron micrographs. Nature Protocols 3, 1941–1974 (2008)
Mindell, J. A. & Grigorieff, N. Accurate determination of local defocus and specimen tilt in electron microscopy. J. Struct. Biol. 142, 334–347 (2003)
Chen, S. et al. High-resolution noise substitution to measure overfitting and validate resolution in 3D structure determination by single particle electron cryomicroscopy. Ultramicroscopy 135, 24–35 (2013)
Heymann, J. B. & Belnap, D. M. Bsoft: image processing and molecular modeling for electron microscopy. J. Struct. Biol. 157, 3–18 (2007)
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004)
Mount, D. W. Using the Basic Local Alignment Search Tool (BLAST). CSH Protoc. 2007, pdb.top17 (2007)
Buchan, D. W., Minneci, F., Nugent, T. C., Bryson, K. & Jones, D. T. Scalable web services for the PSIPRED Protein Analysis Workbench. Nucleic Acids Res. 41, W349–W357 (2013)
Stein, N. CHAINSAW: a program for mutating pdb files used as templates in molecular replacement. J. Appl. Crystallogr. 41, 641–643 (2008)
Winn, M. D. et al. Overview of the CCP4 suite and current developments. Acta Crystallogr. D 67, 235–242 (2011)
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010)
Afonine, P. V. et al. Towards automated crystallographic structure refinement with phenix.refine. Acta Crystallogr. D 68, 352–367 (2012)
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010)
Wang, Z. et al. An atomic model of brome mosaic virus using direct electron detection and real-space optimization. Nature Commun. 5, 4808 (2014)
Zhao, M. et al. Mechanistic insights into the recycling machine of the SNARE complex. Nature 518, 61–67 (2015)
Amunts, A. et al. Structure of the yeast mitochondrial large ribosomal subunit. Science 343, 1485–1489 (2014)
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D 66, 12–21 (2010)
Schrodinger, L. L. C. The PyMOL Molecular Graphics System v.1.3r1. (2010)
Krissinel, E. & Henrick, K. Inference of macromolecular assemblies from crystalline state. J. Mol. Biol. 372, 774–797 (2007)
Hall, T. A. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symposium Series 41, 95–98 (1999)
Wei, Z. et al. Characterization and structure determination of the Cdt1 binding domain of human minichromosome maintenance (Mcm) 6. J. Biol. Chem. 285, 12469–12473 (2010)
We thank X. Li for providing programs in data collection, motion correction and framed-based analysis, and J. Wang for advices on modelling and model refinement. We also thank the National Center for Protein Sciences (Beijing, China) for technical support with cryo-EM data collection and for computation resource. This work was supported by the Ministry of Science and Technology of China (2013CB910404 to N.G.), the National Natural Science Foundation of China (31422016 to N.G.), the Research Grants Council of Hong Kong (GRF664013 and HKUST12/CRF/13G to Yu.Z.) and the Hong Kong University of Science & Technology (B.-K.T.).
The authors declare no competing financial interests.
Extended data figures and tables
a, A flowchart of the procedure for MCM2–7 double hexamer purification from G1 chromatin of the yeast strain MCM4-TEV-3×Flag. b, Fractions taken were analysed by SDS–PAGE and immunoblotting of the indicated MCM subunits. c, The eluted MCM2–7 complexes were subjected to 20–40% glycerol gradient sedimentation at 175,000g for 6.5 h. Collected fractions were analysed by SDS–PAGE and visualized by silver staining. Molecular size markers used are: ALP 140 kDa and thyroglobulin 670 kDa. Fractions 10–12 were pooled and concentrated for cryo-EM analysis. d, A representative raw micrograph of the negatively stained MCM2–7 double hexamer. Representative 2D class averages of negatively stained particles produced by reference-free classification are shown at the top-right corner. The initial 3D model generated using RELION is shown at the bottom-right corner. e, A representative raw micrograph of cryo-EM data. f, Representative 2D class averages of cryo-EM particles from reference-free classification. g, Two typical side views of the average images from f, in enlarged forms, highlighting well-resolved secondary structure elements. Extra densities with poor quality on the two ends of double hexamer could be attributed to the flexible winged-helix motifs (WH) within the CTEs of MCM proteins. h, i, Distribution of particle orientations in the last round of structural refinement, showing in side (h) and top (i) views. The heights of blue cylinders at different projection directions on the surface of a hemisphere are proportional to their particle numbers. Two areas (red asterisks) of a dense equator belt are slightly enriched with particles. j, The density map of the MCM2–7 double hexamer (sharpened) is shown in two views, for the outer (left) and inner (right) surfaces. The map is colour-coded to indicate the range of the local resolution. k, Fourier shell correlation (FSC) curves for the final 3D density map after RELION-based post-processing (red, gold-standard FSC), and for the cross-examination between final atomic model and the 3D density map (blue, final refined model versus map). At a FSC 0.143 cut-off, the overall resolution for the map is 3.8 Å. l, FSC curves for the atomic model cross-validation. See Methods for details.
The sequences of archaeal (SS, Sulfolobus solfataricus) and yeast (Saccharomyces cerevisiae) MCM proteins were aligned using BioEdit73. The alignment was further adjusted manually according to the secondary structure prediction and 3D structural alignment. Conserved hairpins and loops are labelled (H2I, EXT, PS1 and β-turn). CTEs were aligned by the predicted secondary elements in the winged-helix (WH) motifs. Eukaryote-specific sequences (numbered 1–9) well resolved in our structure as in Extended Data Fig. 4a are labelled.
Extended Data Figure 3 Structural diversity of ZFs and structural flexibility of CTEs in the MCM2–7 double hexamer.
a–c, Ribbon representation of ZF motifs of MCM7 (a), MCM3 (b) and MCM5 (c), superimposed with sharpened density map (transparent cyan) at 4σ contour level. Positions of zinc are denoted by red balls. Zinc-binding was not observed in the ZF of MCM3. d, e, Surface representation of the density map (unsharpened, at 1σ contour level) superimposed with colour-coded atomic structures for each MCM subunit, viewed from the CTD ring. Four segmented extra densities are coloured in deep grey (d), with tentative fitting of a winged-helix motif from a crystal structure (PDB code 2KLQ)74 into these four density pieces. e, Same as d, but displayed without extra densities.
a, Schematic illustration of domain organization and subunit-specific features of MCM2–7 subunits, with comparison to the archaeal MCM (SS, Sulfolobus solfataricus) (see also Extended Data Fig. 2). Numbered regions correspond to numbered extensions and insertions highlighted in d–i. ‘-’ symbols denote corresponding regions with reliable densities to trace the main chain direction, but not sufficient for atomic modelling. ‘--’ symbols denote sequences with highly disordered densities. b, c, A protomer of the crystal structure of a chimaeric archaeal MCM hexamer structure (PDB code 4R7Y)30 used as the template for modelling. The archaeal MCM was aligned globally (b) or domain-based flexibly fitted (c) to the atomic model of MCM2. d–i, Side-by-side structural comparison of MCM2–7 proteins, with MCM3-7 globally aligned to the atomic model of MCM2. The well-resolved insertions and extensions of each MCM subunit (d–i) are numbered and coloured in red.
a, Interactions at the CTD ring exemplified by the 7:3 interface. The EXT hairpin of MCM3 facilitates the packing of one helix (the α-linker of the α/β subdomain) from MCM7 with another helix (located at the α subdomain of the CTD) from MCM3. b, Interactions at the neck region, as exemplified by the 6:4 interface. PS1-HP of MCM4 is sandwiched between ACL and H2I-N (N-terminal loop/helix of H2I) of MCM6. At the same time, ACL of MCM6 also interacts with H2I-C (C-terminal helix of H2I) of MCM4. c, Interactions at the NTD ring exemplified by the 6:4 interface. The first loop of OB (OB-L1) that flanks NTD-A, and the extended β-turn loop from MCM6 form a cradle for docking the ZF from MCM4. Asterisks mark sites of strong interactions. d–i, Zoomed-in views of intersubunit interactions between NTD-As of each adjacent MCM pair. The unsharpened density map (transparent grey), contoured at the 2.7σ level, is superimposed with the atomic model. Four of the six MCM proteins (3, 5, 6 and 7) contain NTIs at varying locations of their NTD-As (see also Extended Data Fig. 4). Only the NTI of MCM7 is modelled in our structure. Superimposition of the atomic model with the density map indicates that these NTIs all interact with the NTD-As of the adjacent subunit on the left. Extra densities indicating interactions are marked by red asterisks.
a, Electron microscopy density map (cyan mesh) superimposed with atomic model for NTD-A of MCM7. Two representative α-helices with side chains (right) were displayed in stick representation. b, Electron microscopy density map for the OB and ZF of MCM3. A representative loop of the OB and a strand connecting the OB and ZF with side chains are shown on the right. c, A representative region of inter-hexamer interaction, highlighting the interactions between the β-strands of MCM5-NTE and MCM7-ZF. d, A representative region of intersubunit interaction (MCM4–MCM6), highlighting the hydrophobic interaction between Met342, Phe391 of MCM4 and neighbouring Ile284 of MCM6. e, A representative region of conserved hairpin loops, highlighting H2I of MCM4. Segmented density maps in all panels are displayed at the 5–6σ contour level.
a–f, Outer surface representation of the six subunit interfaces within MCM2–7 single hexamer. a, A unique side channel in the neck region of the M2–M6 interface. The boxed region is shown in a zoomed-in view (right) with individual components (H2I-N, EXT, PS1 and ACL) coloured individually. The size of this side channel is large enough to act as a pore for ssDNA exiting from the central channel during DNA unwinding along with basic residues (Arg566, Lys557 and Lys564) of the EXT hairpin from MCM6. The H2I-N is partially disordered. b–f, Same as a, but at different subunit interfaces. In the case of the 3:5 interface (e), the N–C linker of MCM3 also contributes to the blocking of the channel.
a–f, Zoomed-in views of ATP-binding sites for each MCM dimer. The Walker A and B (WA and WB, respectively) residues of the left subunit, and sensor 3, sensor 2 and arginine finger (AF) residues of the right subunit, are shown in stick model. g, Superimposition of all six active centres. The sensor 3 residues of MCM2 (orange asterisk) and MCM6 (blue asterisk) in the 5:2 and 2:6 dimers display sharply different configurations, resulting in two relatively loose centres. h, i, Superimposition of two representative compact ATPase centres (dimers of 7:3 and 4:7) with that of E1 hexameric helicase (active form)40. j, The ATPase centre (inactive conformation) of an archaeal MCM (PDB code 4R7Y)30. k, l, Superimposition of j with the centres of 2:6 (k) and 7:3 (l). Walker A and B motifs are used as a reference for alignment in all panels. l, A large shift in the sensor 3 of MCM3 is shown by red arrow, compared with the inactive conformation.
a–f, Zoomed-in views of the active centres for all MCM subunit pairs. The conserved ATPase elements of the active centres are labelled. Segmented nucleotide densities at a contour level of 5.5σ were superimposed (transparent grey). Note that nucleotide occupancies at the centres of 6:4 and 3:5 are relatively low. For the 7:3 dimer, there seems to be extra density for γ-phosphate or Mg2+, but could not be confirmed at the current resolution (3.8 Å). Nucleotides were modelled using ADP.
The cryo-EM density map (unsharpened) of the MCM2-7 DH is first shown in surface representation, followed by superimposition of atomic models for each of the MCM proteins one by one. The unique side-channel between MCM2 and MCM6 is highlighted. Subsequently, only the two rings of ZFs, with their atomic models converted to surface representation, are shown in zoom-in views. The two stacked ZF rings are rotated in different directions to highlight the diameter and wall components of a major channel and two minor channels at the DH interface. At last, the surface representation of two ZF pairs of MCM2:MCM5 is hidden, highlighting the proposed fusion of three channels into a larger one upon the gap opening between MCM2 and MCM5. A thumbnail map of the MCM2-7 DH, with the 2-fold axis displayed as a red rod, is shown on the top right corner to illustrate the orientations of individual movie frames relative to the DH. (MP4 18712 kb)
The cryo-EM density map of the MCM2-7 DH (sharpened) is displayed in surface representation, zoomed into selected regions with atomic models superimposed. (MP4 20759 kb)
About this article
Cite this article
Li, N., Zhai, Y., Zhang, Y. et al. Structure of the eukaryotic MCM complex at 3.8 Å. Nature 524, 186–191 (2015). https://doi.org/10.1038/nature14685
Structural mechanism for the selective phosphorylation of DNA-loaded MCM double hexamers by the Dbf4-dependent kinase
Nature Structural & Molecular Biology (2022)
The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer
Nature Communications (2022)
Nature Communications (2022)
Cell Discovery (2022)