Papers

Jobbins, A. M., Yu, S., Paterson, H. A. B., Maude, H., Kefala-Stavridi, A., Speck, C., Cebola, I., Vernia, S. (2023).  Pre-RNA splicing in metabolic homeostasis and liver disease.  Trends in Endocrinology & Metabolism, (in the Press).
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Saleh, A., Noguchi, Y., Aramayo, R., Ivanova, M. E., Stevens, K. M., Montoya, A., Sunidhi, S., Carranza, N. L., Skwark, M. J., Speck, C. (2022).  The structural basis of Cdc7-Dbf4 kinase dependent targeting and phosphorylation of the MCM2-7 double hexamer.  Nature Communication 13:2915.
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Feng, X., Noguchi, Y., Barbon, M., Stillman, B., Speck, C., Li, H. (2021).  The structure of ORC-Cdc6 on an origin DNA reveals the mechanism of ORC activation by the replication initiator Cdc6.  Nature Communications 12:3883.
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Hu, Y., Tareen, A., Sheu, Y. J., Ireland, W.T ., Speck, C., Li, H., Joshua-Tor, L., Kinney, J. B., Stillman, B. (2020).  Evolution of DNA replication origin specification and gene silencing mechanisms.  Nature Communications 11:5175.
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Roman-Trufero, M., Ito, C. M., Pedebos, C., Magdalou, I., Wang, Y.-F., Karimi, M. M., Moyon, B., Webster, Z., di Gregorio, A., Azuara, V., Khalid, S., Speck, C., Rodriguez, T., Dillon, N. (2020).  Evolution of an amniote-specific mechanism for modulating ubiquitin signalling via phosphoregulation of the E2 enzyme UBE2D3.  Molecular Biology and Evolution 37, 1986-2001.
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Yuan, Z., Schneider, S., Dodd, T., Riera, A., Bai, L., Yan, C., Magdalou, I., Ivanov, I., Stillman, B., Li, H., Speck, C. (2020).  Structural mechanism of helicase loading onto replication origin DNA by ORC-Cdc6.  Proceedings of the National Academy of Sciences of the United States of America 117, 17747-17756.
AbstractFull text | Correction |

Mendes, M. L., Fischer, L., Chen, Z. A., Barbon, M., O’Reilly, F. J., Giese, S. H., Bohlke-Schneider, M., Belsom, A., Dau, T., Combe, C. W., Graham, M., Eisele, M. R., Baumeister, W., Speck, C., Rappsilber, J. (2019).  An integrated workflow for crosslinking mass spectrometry.  Molecular Systems Biology 15, e8994.
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Yu, Y., Schleich, K., Yue, B., Ji, S., Lohneis, P., Kemper, K., Silvis, M. R., Qutob, N., van Rooijen, E., Werner-Klein, M., Li, L., Dhawan, D., Meierjohann, S., Reimann, M., Elkahloun, A., Treitschke, S., Dörken, B., Speck, C., Mallette, F. A., Zon, L. I., Holmen, S. L., Peeper, D. S., Samuels, Y., Schmitt, C. A., Lee, S. (2018). Targeting the senescence-overriding cooperative activity of structurally unrelated H3K9 demethylases in melanoma. Cancer Cell 33, 322-336.
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Noguchi, Y., Yuan, Z., Bai, L., Schneider, S., Zhao, G., Stillman, B., Speck, C., Li, H. (2017). Cryo-EM structure of Mcm2-7 double hexamer on DNA suggests a lagging-strand DNA extrusion model. Proceedings of the National Academy of Sciences of the United States of America 114, E9529-E9538.
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Riera, A., Barbon, M., Noguchi, Y., Reuter, L. M., Schneider, S., Speck, C. (2017). From structure to mechanism — understanding initiation of DNA replication. Genes & Development 31, 1073-1078.
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Yuan, Z., Riera, A., Bai, L., Sun, J., Nandi, S., Spanos, C., Chen, Z. A., Barbon, M., Rappsilber, J., Stillman, B., Speck, C., Li, H. (2017). Structural basis of Mcm2–7 replicative helicase loading by ORC–Cdc6 and Cdt1. Nature Structure & Molecular Biology 24, 316-324.
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Speck, C. (2016). Exceeding the limits – Cdc45 overexpression turns bad. Cell Cycle 15, 1809-1810.
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Tognetti, S., Speck, C. (2016). Replicating repetitive DNA. Nature Cell Biology 18, 593-594.
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Chang, F., Riera, A., Evrin, C., Sun, J., Li, H., Speck, C., Weinreich, M. (2015). Cdc6 ATPase activity disengages Cdc6 from the pre-replicative complex to promote DNA replication. eLife 4, e05759.
Abstract | Full text | Biomedical Picture of the Day | MRC Clinical Sciences Centre News | Imperial College London News

Herrera, M. C.*, Tognetti, S.*, Riera, A., Zech, J., Clarke, P., Fernández-Cid, A., Speck, C. (2015). A reconstituted system reveals how activating and inhibitory interactions control DDK dependent assembly of the eukaryotic replicative helicase. Nucleic Acids Research 43, 10238-10250.
*Shared first authorship
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Riera, A., Speck, C. (2015). MCM2-7 – Opening the gate to DNA Replication. Cell Cycle 14, 6-8.
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Tognetti, S., Riera, A., Speck, C. (2015) Switch on the engine: how the eukaryotic replicative MCM2–7 helicase becomes activated. Chromosoma 124, 13-26.
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Evrin, C.*, Fernández-Cid, A.*, Riera, A., Zech, J., Clarke, P., Herrera, M. C., Tognetti, S., Lurz, R., Speck, C. (2014). The ORC/Cdc6/MCM2-7 complex facilitates MCM2-7 dimerization during pre-replicative complex formation. Nucleic Acids Research 42, 2257-2269.
*Shared first authorship
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Riera, A., Tognetti, S., Speck, C. (2014). Helicase loading: How to build a MCM2-7 double-hexamer. Seminars in Cell & Developmental Biology 30C, 104-109.
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Samel, S. A., Fernández-Cid, A., Sun, J., Riera, A., Tognetti, S., Herrera, C., Li, H., Speck, C. (2014). A unique DNA entry gate serves for regulated loading of the eukaryotic replicative helicase MCM2–7 onto DNA. Genes & Development 28, 1653-1666.
Abstract | Imperial College London News |

Silva, N., Ferrandiz, N., Barroso, C., Tognetti, S., Lightfoot, J., Telecan, O., Encheva, V., Faull, P., Hanni, S., Furger, A., Snidjers, A. P., Speck, C., Martinez-Perez, E. (2014). The fidelity of synaptonemal complex assembly is regulated by a signaling mechanism that controls early meiotic progression. Developmental Cell 31, 503-511.
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Sun, J.*, Fernandez-Cid, A.*, Riera, A.*, Tognetti, S., Yuan, Z., Stillman, B.†, Speck, C.†, Li, H.† (2014). Structural and mechanistic insights into Mcm2–7 double-hexamer assembly and function. Genes & Development 28, 2291-2303.
*Shared first authorship, †Corresponding authors
Abstract | Biomedical Picture of the Day |

Evrin, C., Fernández-Cid, A., Zech, J., Herrera, M. C., Riera, A., Clarke, P., Brill, S., Lurz, R., Speck, C. (2013). In the absence of ATPase activity, pre-RC formation is blocked prior to MCM2–7 hexamer dimerization. Nucleic Acids Research 41, 3162-3172.
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Fernández-Cid, A.*, Riera, A.*, Tognetti, S., Herrera, M. C., Samel, S., Evrin, C., Winkler, C., Gardenal, E., Uhle. S., Speck, C. (2013). An ORC/Cdc6/MCM2-7 complex is formed in a multistep reaction to serve as a platform for MCM double-hexamer formation. Molecular Cell 50, 577-588.
*Shared first authorship
Abstract | Full text | Molecular Cell Preview |

Riera, A., Fernández-Cid, A., Speck, C. (2013). The ORC/Cdc6/MCM2–7 complex, a new power player for regulated helicase loading. Cell Cycle 12, 2155-2156.
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Riera, A., Li, H., Speck, C. (2013). Seeing is believing: The MCM2–7 helicase trapped in complex with its DNA loader. Cell Cycle 12, 2917-2918.
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Sun, J.*, Evrin, C.*, Samel, S. A., Fernández-Cid, A., Riera, A., Kawakami, H., Stillman, B.†, Speck, C.†, Li, H.† (2013). Cryo-EM structure of a helicase loading intermediate containing ORC–Cdc6–Cdt1–MCM2-7 bound to DNA. Nature Structural & Molecular Biology 20, 944-951.
*Shared first authorship; †Corresponding authors
Abstract | Full text | Brookhaven National Laboratory Newsroom |

Sun, J., Kawakami, H., Zech, J., Speck, C., Stillman, B., Li, H. (2012). Cdc6-induced conformational changes in ORC bound to origin DNA revealed by cryo-electron microscopy. Structure 20, 534-544.
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Johansson, E., Speck, C. and Chabes, A. (2011). A top-down view on DNA replication and recombination from 9,000 feet above sea level. Genome Biology 12, 304.
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Evrin, C., Clarke, P., Zech, J., Lurz, R., Sun, J., Uhle, S., Li, H., Stillman, B., Speck, C. (2009). A double-hexameric MCM2-7 complex is loaded onto origin DNA during licensing of eukaryotic DNA. Proceedings of the National Academy of Sciences of the United States of America 106, 20240-20245.
Abstract | Full text | F1000Prime |

Chen, Z.*, Speck, C.*, Wendel, P., Tang, C., Stillman, B., Li, H. (2008). The architecture of the DNA replication origin recognition complex in Saccharomyces cerevisiae. Proceedings of the National Academy of Sciences of the United States of America 105, 10326-10331.
*Contributed equally to work
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Majka, J., Speck, C. (2007). Analysis of protein-DNA interactions using surface plasmon resonance. Advances in Biochemical Engineering/Biotechnology 104, 13-36.
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Speck, C., Stillman, B. (2007). Cdc6 ATPase activity regulates ORC-Cdc6 stability and the selection of specific DNA sequences as origins of DNA replication. The Journal of Biological Chemistry 282, 11705-11714.
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Speck, C., Chen, Z., Li, H., Stillman, B. (2005). ATPase-dependent cooperative binding of ORC and Cdc6 to origin DNA. Nature Structural & Molecular Biology 12, 965-971.
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de la Hoz, A. B., Pratto, F., Misselwitz, R., Speck, C., Weihofen, W., Welfle, K., Saenger, W., Welfle, H., Alonso, J. C. (2004). Recognition of DNA by ω protein from the broad-host range Streptococcus pyogenes plasmid pSM19035: analysis of binding to operator DNA with one to four heptad repeats. Nucleic Acids Research 32, 3136-3147.

Berenstein, D., Olesen, K., Speck, C. , Skovgaard, O. (2002). Genetic organization of the Vibrio harveyi dnaA gene region and analysis of the function of the V. harveyi DnaA protein in Escherichia coli. Journal of Bacteriology 184, 2533-2538.
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Pieper, U., Groll, D. H., Wünsch, S., Gast, F.-U., Speck, C., Mücke, N., Pingoud, A. (2002). The GTP-dependent restriction enzyme McrBC from Escherichia coli forms high-molecular mass complexes with DNA and produces a cleavage pattern with a characteristic 10-base pair repeat. Biochemistry 41, 5245-5254.
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Messer, W., Blaesing, F., Jakimowicz, D., Krause, M., Majka, J., Nardmann, J., Schaper, S., Seitz, H., Speck, C., Weigel, C., Wegrzyn, G., Welzeck, M., Zakrzewska-Czerwinska, J. (2001). Bacterial replication initiator DnaA. Rules for DnaA binding and roles of DnaA in origin unwinding and helicase loading. Biochimie 83, 5-12.
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Speck, C., Messer, W. (2001). Mechanism of origin unwinding: sequential binding of DnaA to double- and single-stranded DNA. The EMBO Journal 20, 1469-1476.
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Schaper, S., Nardmann, J., Lüder, G., Lurz, R., Speck, C., Messer, W. (2000). Identification of the chromosomal replication origin from Thermus thermophilus and its interaction with the replication initiator DnaA. Journal of Molecular Biology 299, 655-665.
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Skarstad, K., Lueder, G., Lurz, R., Speck, C., Messer, W. (2000). The Escherichia coli SeqA protein binds specifically and co-operatively to two sites in hemimethylated and fully methylated oriC. Molecular Microbiology 36, 1319-1326.
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Köhler, M., Speck, C., Christiansen, M., Bischoff, F. R., Prehn, S., Haller, H., Görlich, D., Hartmann, E. (1999). Evidence for distinct substrate specificities of importin α-family members in nuclear protein import. Molecular and Cellular Biology 19, 7782-7791.
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Messer, W., Blaesing, F., Majka, J., Nardmann, J., Schaper, S., Schmidt, A., Seitz, H., Speck, C., Tüngler, D., Wegrzyn, G., Weigel, C., Welzeck, M., Zakrzewska-Czerwinska, J. (1999). Functional domains of DnaA proteins. Biochimie 81, 819-825.
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Speck, C., Weigel, C., Messer, W. (1999). ATP- and ADP-DnaA protein, a molecular switch in gene regulation. The EMBO Journal 18, 6169-6176.
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Jakimowicz, D., Majka, J., Messer, W., Speck, C., Fernandez, M., Martin, M. C., Sanchez, J., Schauwecker, F., Keller, U., Schrempf, H., Zakrzewska-Czerwinska, J. (1998). Structural elements of the Streptomyces oriC region and their interactions with the DnaA protein. Microbiology 144, 1281-1290.
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Szalewska-Palasz, A., Weigel, C., Speck, C., Srutkowska, S., Konopa, G., Lurz, R., Marszalek, J., Taylor, K., Messer, W., Wegrzyn, G. (1998). Interaction of the Escherichia coli DnaA protein with bacteriophage λ DNA. Molecular and General Genetics 259, 679-688.
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Speck, C., Weigel, C., Messer, W. (1997). From footprint to toeprint: a close-up of the DnaA box, the binding site for the bacterial initiator protein DnaA. Nucleic Acids Research 5, 3242-3247.
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