Multiple mechanisms for licensing human replication origins – Nature
Bleichert, F. Mechanisms of replication origin licensing: a structural perspective. Curr. Opin. Struct. Biol. 59, 195–204 (2019).
Google Scholar
Lewis, J. S. & Costa, A. Caught in the act: structural dynamics of replication origin activation and fork progression. Biochem. Soc. Trans. 48, 1057–1066 (2020).
Google Scholar
Greiwe, J. F., Zanetti, G., Miller, T. C. R. & Costa, A. In silico reconstitution of DNA replication. Lessons from single-molecule imaging and cryo-tomography applied to single-particle cryo-EM. Curr. Opin. Struct. Biol. 72, 279–286 (2022).
Google Scholar
Costa, A. & Diffley, J. F. X. The initiation of eukaryotic DNA replication. Annu. Rev. Biochem. 91, 107–131 (2022).
Google Scholar
Miller, T. C. R., Locke, J., Greiwe, J. F., Diffley, J. F. X. & Costa, A. Mechanism of head-to-head MCM double-hexamer formation revealed by cryo-EM. Nature 575, 704–710 (2019).
Google Scholar
Gupta, S., Friedman, L. J., Gelles, J. & Bell, S. P. A helicase-tethered ORC flip enables bidirectional helicase loading. eLife 10, e74282 (2021).
Google Scholar
Parker, M. W., Botchan, M. R. & Berger, J. M. Mechanisms and regulation of DNA replication initiation in eukaryotes. Crit. Rev. Biochem. Mol. Biol. 52, 107–144 (2017).
Google Scholar
Remus, D. et al. Concerted loading of Mcm2–7 double hexamers around DNA during DNA replication origin licensing. Cell 139, 719–730 (2009).
Google Scholar
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).
Google Scholar
Gambus, A., Khoudoli, G. A., Jones, R. C. & Blow, J. J. MCM2–7 form double hexamers at licensed origins in Xenopus egg extract. J. Biol. Chem. 286, 11855–11864 (2011).
Google Scholar
Bell, S. P. & Stillman, B. ATP-dependent recognition of eukaryotic origins of DNA replication by a multiprotein complex. Nature 357, 128–134 (1992).
Google Scholar
Li, N. et al. Structure of the origin recognition complex bound to DNA replication origin. Nature 559, 217–222 (2018).
Google Scholar
Speck, C., Chen, Z., Li, H. & Stillman, B. ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nat. Struct. Mol. Biol. 12, 965–971 (2005).
Google Scholar
Sun, J. et al. Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2–7 bound to DNA. Nat. Struct. Mol. Biol. 20, 944–951 (2013).
Google Scholar
Yuan, Z. et al. Structural basis of Mcm2–7 replicative helicase loading by ORC–Cdc6 and Cdt1. Nat. Struct. Mol. Biol. 24, 316–324 (2017).
Google Scholar
Kang, S., Warner, M. D. & Bell, S. P. Multiple functions for Mcm2-7 ATPase motifs during replication initiation. Mol. Cell 55, 655–665 (2014).
Google Scholar
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).
Google Scholar
Ticau, S. et al. Mechanism and timing of Mcm2–7 ring closure during DNA replication origin licensing. Nat. Struct. Mol. Biol. 24, 309–315 (2017).
Google Scholar
Amasino, A. L., Gupta, S., Friedman, L. J., Gelles, J. & Bell, S. P. Regulation of replication origin licensing by ORC phosphorylation reveals a two-step mechanism for Mcm2–7 ring closing. Proc. Natl Acad. Sci. USA 120, e2221484120 (2023).
Google Scholar
Vashee, S. et al. Sequence-independent DNA binding and replication initiation by the human origin recognition complex. Genes Dev. 17, 1894–1908 (2003).
Google Scholar
Remus, D., Beall, E. L. & Botchan, M. R. DNA topology, not DNA sequence, is a critical determinant for Drosophila ORC–DNA binding. EMBO J. 23, 897–907 (2004).
Google Scholar
Dhar, S. K., Delmolino, L. & Dutta, A. Architecture of the human origin recognition complex. J. Biol. Chem. 276, 29067–29071 (2001).
Google Scholar
Vashee, S., Simancek, P., Challberg, M. D. & Kelly, T. J. Assembly of the human origin recognition complex. J. Biol. Chem. 276, 26666–26673 (2001).
Google Scholar
Bleichert, F. et al. A Meier-Gorlin syndrome mutation in a conserved C-terminal helix of Orc6 impedes origin recognition complex formation. eLife 2, e00882 (2013).
Google Scholar
Gillespie, P. J., Li, A. & Blow, J. J. Reconstitution of licensed replication origins on Xenopus sperm nuclei using purified proteins. BMC Biochem. 2, 15 (2001).
Google Scholar
Li, J. et al. The human pre-replication complex is an open complex. Cell 186, 98–111 (2023).
Google Scholar
Noguchi, Y. et al. Cryo-EM structure of Mcm2–7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. Proc. Natl Acad. Sci. USA 114, E9529–E9538 (2017).
Google Scholar
Abid Ali, F. et al. Cryo-EM structure of a licensed DNA replication origin. Nat. Commun. 8, 2241 (2017).
Google Scholar
Schmidt, J. M. & Bleichert, F. Structural mechanism for replication origin binding and remodeling by a metazoan origin recognition complex and its co-loader Cdc6. Nat. Commun. 11, 4263 (2020).
Google Scholar
Parker, M. W. et al. A new class of disordered elements controls DNA replication through initiator self-assembly. eLife 8, e48562 (2019).
Google Scholar
Hossain, M., Bhalla, K. & Stillman, B. Multiple, short protein binding motifs in ORC1 and CDC6 control the initiation of DNA replication. Mol. Cell 81, 1951–1969 (2021).
Google Scholar
Wohlschlegel, J. A. et al. Inhibition of eukaryotic DNA replication by geminin binding to Cdt1. Science 290, 2309–2312 (2000).
Google Scholar
Tada, S., Li, A., Maiorano, D., Mechali, M. & Blow, J. J. Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nat. Cell Biol. 3, 107–113 (2001).
Google Scholar
Shibata, E. et al. Two subunits of human ORC are dispensable for DNA replication and proliferation. eLife 5, e19084 (2016).
Google Scholar
Shibata, E. & Dutta, A. A human cancer cell line initiates DNA replication normally in the absence of ORC5 and ORC2 proteins. J. Biol. Chem. 295, 16949–16959 (2020).
Google Scholar
Lin, Y. C. et al. Orc6 is a component of the replication fork and enables efficient mismatch repair. Proc. Natl Acad. Sci. USA 119, e2121406119 (2022).
Google Scholar
Chou, H. C. et al. The human origin recognition complex is essential for pre-RC assembly, mitosis, and maintenance of nuclear structure. eLife 10, e61797 (2021).
Google Scholar
Chen, S., de Vries, M. A. & Bell, S. P. Orc6 is required for dynamic recruitment of Cdt1 during repeated Mcm2-7 loading. Genes Dev. 21, 2897–2907 (2007).
Google Scholar
Frigola, J., Remus, D., Mehanna, A. & Diffley, J. F. ATPase-dependent quality control of DNA replication origin licensing. Nature 495, 339–343 (2013).
Google Scholar
Fernandez-Cid, A. et al. An ORC/Cdc6/MCM2–7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer assembly. Mol. Cell 50, 577–588 (2013).
Google Scholar
Wisniewski, J. R., Hein, M. Y., Cox, J. & Mann, M. A. “Proteomic ruler” for protein copy number and concentration estimation without spike-in standards. Mol. Cell Proteomics 13, 3497–3506 (2014).
Google Scholar
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).
Google Scholar
Yuan, Z. et al. Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6. Proc. Natl Acad. Sci. USA 117, 17747–17756 (2020).
Google Scholar
Nielsen-Dandoroff, E., Ruegg, M. S. G. & Bicknell, L. S. The expanding genetic and clinical landscape associated with Meier–Gorlin syndrome. Eur. J. Hum. Genet. 31, 859–868 (2023).
Google Scholar
Li, J. et al. A boy with Meier–Gorlin syndrome carrying a novel ORC6 mutation and uniparental disomy of chromosome 16. Zhonghua Yi Xue Yi Chuan Xue Za Zhi 34, 68–72 (2017).
Google Scholar
Bicknell, L. S. et al. Mutations in the pre-replication complex cause Meier–Gorlin syndrome. Nat. Genet. 43, 356–359 (2011).
Google Scholar
Ticau, S., Friedman, L. J., Ivica, N. A., Gelles, J. & Bell, S. P. Single-molecule studies of origin licensing reveal mechanisms ensuring bidirectional helicase loading. Cell 161, 513–525 (2015).
Google Scholar
Weissmann, F. et al. MCM double hexamer loading visualised with human proteins. Preprint at bioRxiv https://doi.org/10.1101/2024.04.10.588848 (2024).
Wells, J. N. et al. Reconstitution of human DNA licensing and the structural and functional analysis of key intermediates. Preprint at bioRxiv https://doi.org/10.1101/2024.04.11.589023 (2024).
Coster, G. & Diffley, J. F. X. Bidirectional eukaryotic DNA replication is established by quasi-symmetrical helicase loading. Science 357, 314–318 (2017).
Google Scholar
Sanchez, H. et al. DNA replication origins retain mobile licensing proteins. Nat. Commun. 12, 1908 (2021).
Google Scholar
Zhang, A., Friedman, L. J., Gelles, J. & Bell, S. P. Changing protein-DNA interactions promote ORC binding-site exchange during replication origin licensing. Proc. Natl Acad. Sci. USA 120, e2305556120 (2023).
Google Scholar
Stiff, T. et al. Deficiency in origin licensing proteins impairs cilia formation: implications for the aetiology of Meier–Gorlin syndrome. PLoS Genet. 9, e1003360 (2013).
Google Scholar
Balasov, M., Akhmetova, K. & Chesnokov, I. Drosophila model of Meier–Gorlin syndrome based on the mutation in a conserved C-Terminal domain of Orc6. Am. J. Med. Genet. A 167A, 2533–2540 (2015).
Google Scholar
Nguyen, V. Q., Co, C. & Li, J. J. Cyclin-dependent kinases prevent DNA re-replication through multiple mechanisms. Nature 411, 1068–1073 (2001).
Google Scholar
Lim, C. T. et al. Cell cycle regulation has shaped budding yeast replication origin structure and function. Preprint at bioRxiv https://doi.org/10.1101/2024.01.10.575016 (2024).
Xu, N. et al. Cryo-EM structure of human hexameric MCM2-7 complex. iScience 25, 104976 (2022).
Google Scholar
Champasa, K., Blank, C., Friedman, L. J., Gelles, J. & Bell, S. P. A conserved Mcm4 motif is required for Mcm2–7 double-hexamer formation and origin DNA unwinding. eLife 8, e45538 (2019).
Google Scholar
Gradia, S. D. et al. MacroBac: new technologies for robust and efficient large-scale production of recombinant multiprotein complexes. Methods Enzymol. 592, 1–26 (2017).
Google Scholar
Mastronarde, D. N. Automated electron microscope tomography using robust prediction of specimen movements. J. Struct. Biol. 152, 36–51 (2005).
Google Scholar
Zhang, K. Gctf: real-time CTF determination and correction. J. Struct. Biol. 193, 1–12 (2016).
Google Scholar
Kimanius, D., Dong, L., Sharov, G., Nakane, T. & Scheres, S. H. W. New tools for automated cryo-EM single-particle analysis in RELION-4.0. Biochem. J 478, 4169–4185 (2021).
Google Scholar
Punjani, A., Rubinstein, J. L., Fleet, D. J. & Brubaker, M. A. cryoSPARC: algorithms for rapid unsupervised cryo-EM structure determination. Nat. Methods 14, 290–296 (2017).
Google Scholar
Jaremko, M. J., On, K. F., Thomas, D. R., Stillman, B. & Joshua-Tor, L. The dynamic nature of the human origin recognition complex revealed through five cryoEM structures. eLife 9, e58622 (2020).
Google Scholar
Pettersen, E. F. et al. UCSF Chimera–a visualization system for exploratory research and analysis. J. Comput. Chem. 25, 1605–1612 (2004).
Google Scholar
Goddard, T. D., Huang, C. C. & Ferrin, T. E. Visualizing density maps with UCSF Chimera. J. Struct. Biol. 157, 281–287 (2007).
Google Scholar
Cheng, K., Wilkinson, M., Chaban, Y. & Wigley, D. B. A conformational switch in response to Chi converts RecBCD from phage destruction to DNA repair. Nat. Struct. Mol. Biol. 27, 71–77 (2020).
Google Scholar
Punjani, A., Zhang, H. & Fleet, D. J. Non-uniform refinement: adaptive regularization improves single-particle cryo-EM reconstruction. Nat. Methods 17, 1214–1221 (2020).
Google Scholar
Sanchez-Garcia, R. et al. DeepEMhancer: a deep learning solution for cryo-EM volume post-processing. Commun. Biol. 4, 874 (2021).
Google Scholar
Scheres, S. H. & Chen, S. Prevention of overfitting in cryo-EM structure determination. Nat. Methods 9, 853–854 (2012).
Google Scholar
Tan, Y. Z. et al. Addressing preferred specimen orientation in single-particle cryo-EM through tilting. Nat. Methods 14, 793–796 (2017).
Google Scholar
Emsley, P., Lohkamp, B., Scott, W. G. & Cowtan, K. Features and development of Coot. Acta Crystallogr. D 66, 486–501 (2010).
Google Scholar
Adams, P. D. et al. PHENIX: a comprehensive Python-based system for macromolecular structure solution. Acta Crystallogr. D 66, 213–221 (2010).
Google Scholar
Afonine, P. V. et al. Real-space refinement in PHENIX for cryo-EM and crystallography. Acta Crystallogr. D 74, 531–544 (2018).
Google Scholar
Chen, V. B. et al. MolProbity: all-atom structure validation for macromolecular crystallography. Acta Crystallogr. D. 66, 12–21 (2010).
Google Scholar
Zivanov, J., Nakane, T. & Scheres, S. H. W. A Bayesian approach to beam-induced motion correction in cryo-EM single-particle analysis. IUCrJ 6, 5–17 (2019).
Google Scholar
Rohou, A. & Grigorieff, N. CTFFIND4: Fast and accurate defocus estimation from electron micrographs. J. Struct. Biol. 192, 216–221 (2015).
Google Scholar
Goddard, T. D. et al. UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci. 27, 14–25 (2018).
Google Scholar
Evans, R. et al. Protein complex prediction with AlphaFold-Multimer. Preprint at bioRxiv https://doi.org/10.1101/2021.10.04.463034 (2022).
Schmid, E. W. & Walter, J. C. Predictomes: a classifier-curated database of AlphaFold-modeled protein-protein interactions. Preprint at bioRxiv https://doi.org/10.1101/2024.04.09.588596 (2024).
Abramson, J. et al. Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature 630, 493–500 (2024).
Google Scholar
Kawasaki, Y., Kim, H. D., Kojima, A., Seki, T. & Sugino, A. Reconstitution of Saccharomyces cerevisiae prereplicative complex assembly in vitro. Genes Cells 11, 745–756 (2006).
Google Scholar
Wu, M., Lu, W., Santos, R. E., Frattini, M. G. & Kelly, T. J. Geminin inhibits a late step in the formation of human pre-replicative complexes. J. Biol. Chem. 289, 30810–30821 (2014).
Google Scholar
