Dr Owen Davies
Wellcome Senior Research Fellow
Contact details
- Email: owen.davies@ed.ac.uk
Address
- Street
-
Wellcome Centre for Cell Biology
Institute of Cell Biology
University of Edinburgh
Michael Swann Building
Max Born Crescent
Edinburgh - City
- Post code
- EH9 3BF
Background
2021-2026 Wellcome Senior Research Fellow
Institute of Cell Biology, University of Edinburgh
2014-2020 Wellcome Trust and Royal Society Sir Henry Dale Fellow
Institute for Cell and Molecular Biosciences, Newcastle University
2010-2013 Post-Doctoral Research Associate
Department of Biochemistry, University of Cambridge
2007-2009 Royal Commission for the Exhibition of 1851 Research Fellow
Institute for Stem Cell Research, University of Edinburgh
Qualifications
2007 PhD in Biochemistry
Department of Biochemistry, University of Cambridge
2003 BSc (Hons.) First Class in Medical Science
University of St. Andrews
Research summary
Structural biology of meiosis
Meiotic cell division is defined by a unique and highly dynamic programme of events that results in homologous chromosome segregation following crossover formation. In mammals, the telomeric ends of chromosomes become tethered to the nuclear envelope by the meiotic telomere complex, where they undergo rapid movements, driven by microtubule forces transmitted by the LINC complex, that facilitate the identification and alignment of homologous chromosome pairs through recombination. Once established, homologue chromosome pairs become synapsed along their length by the zipper-like assembly of the synaptonemal complex, which provides the unique three-dimensional architecture necessary for recombination intermediate resolution and crossover formation. Our research aims to uncover the structure, assembly mechanism and recombination function of the synaptonemal complex, the mechanistic basis of nuclear envelope tethering by the meiotic telomere complex and the mechanism of force transduction by the LINC complex. To achieve this, we adopt a structural biology approach of biophysics, crystallography and cryo-EM, coupled with collaborative structure-directed mutation in mouse meiosis. Ultimately, we aim to uncover how the mammalian synaptonemal complex, meiotic telomere complex and LINC complex operate together as an integrated molecular machine to achieve their essential functions of mammalian meiosis, and crucially how their dysfunction leads to human infertility, miscarriage and aneuploidy.
2024
Gurusaran, M., Erlandsen, B.S. & Davies, O.R. (2024) The crystal structure of SUN1-KASH6 reveals an asymmetric LINC complex architecture compatible with nuclear membrane insertion. Communications Biology, In press.
Weber, J., Legal, T., Lezcano, A.P., Gluszek, A., Paterson, C., Eibes, S., Barisic, M., Davies, O.R. & Welburn, J.P.I. (2024) A conserved CENP-E region mediates BubR1-independent recruitment to the outer corona at mitotic onset. Current Biology, In press.
2023
Billmyre, K.K., Kesler, E.A., Tsuchiya, D., Corbin, T.J., Weaver, K., Moran, A., Yu, Z., Adams, L., Delventhal, K., Durnin, M., Davies, O.R.* & Hawley, R.S.* (2023) SYCP1 head-to-head assembly is required for chromosome synapsis in mouse meiosis. Science Advances, 9 (42), eadi156. https://doi.org/10.1126/sciadv.adi1562
Gurusaran, M., Biemans, J.J, Wood, C.W. & Davies, O.R. (2023) Molecular insights into LINC complex architecture through the crystal structure of a luminal trimeric coiled-coil domain of SUN1. Frontiers in Cell and Developmental Biology, 11, 1144277. https://doi.org/10.3389/fcell.2023.1144277
Adams, I.R. & Davies, O.R. (2023) Meiotic Chromosome Structure, the Synaptonemal Complex and Infertility. Annual Review of Genomics and Human Genetics, 24. https://doi.org/10.1146/annurev-genom-110122-090239
Alexander, L., Durairaj, J, Kryshtafovych, A., . . . , Davies, O.R., . . . , Moult, J. & Schwede, T. (2023) Protein target highlights in CASP15: Analysis of models by structure providers. Proteins, 1‐29. https://doi.org/10.1002/prot.26545
Garner, K.E.L., Salter, A., Lau, C.K., Gurusaran, M., Villemant, C., Granger, E.P., McNee, G., Woodman, P.G., Davies, O.R., Burke, B.E., Allan, V.J. (2023) The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein. Journal of Cell Biology, 222 (5), e202204042. https://doi.org/10.1083/jcb.202204042
Crichton, J.H., Dunce, J.M., Dunne, O.M., Salmon, L.J., Devenney, P.S., Lawson, J., Adams, I.R. & Davies, O.R. (2023) Structural maturation of SYCP1-mediated meiotic chromosome synapsis by SYCE3. Nature Structural and Molecular Biology, 30, 188-199. https://doi.org/10.1038/s41594-022-00909-1
2022
Dunce, J.M., Salmon, L.J. & Davies, O.R. (2022) Coiled-coil structure of meiosis protein TEX12 and conformational regulation by its C-terminal tip. Communications Biology, 5, 921. https://doi.org/10.1038/s42003-022-03886-9
2021
Sandhu, S., Sou, E.I.F., Hunter, J.E., Salmon, L., Wilson, C.L., Perkins, N.D., Hunter, N., Davies, O.R. & McClurg, U.L. (2021) Centrosome dysfunction associated with somatic expression of the synaptonemal complex protein TEX12. Communications Biology, 4, 1371. https://doi.org/10.1038/s42003-021-02887-4
Dunce, J.M., Salmon, L.J. & Davies, O.R. (2021) Structural basis of meiotic chromosome synaptic elongation through hierarchical fibrous assembly of SYCE2-TEX12. Nature Structural and Molecular Biology, 28, 681-693. https://doi.org/10.1038/s41594-021-00636-z
Thomas, C., Wetherall, B., Levasseur, M.D., Harris, R.J., Kerridge, S.T., Higgins, J.M.G., Davies, O.R. & Madgwick, S. (2021) A prometaphase mechanism of securin destruction is essential for meiotic progression in mouse oocytes. Nature Communications, 12, 4322. https://doi.org/10.1038/s41467-021-24554-2
Morton, C.R., Rzechorzek, N.J., Maman, J.D., Kuramochi, M., Sekiguchi, H., Rambo, R., Sasaki, Y.C., Davies, O.R. & Pellegrini, L. (2021) Structural basis for the coiled-coil architecture of human CtIP. Open Biology, 11 (6), 210060. https://doi.org/10.1098/rsob.210060
Bhagwat, N.R., Owens, S.N., Ito, M., Boinapalli, J.V., Poa, P., Ditzel, A., Kopparapu, S., Mahalawat, M., Davies, O.R., Collins, S.R., Johnson, J.R., Krogan, N.J. & Hunter, N. (2021) SUMO is a pervasive regulator of meiosis. eLife, 10, e57720. https://doi.org/10.7554/eLife.57720
Gurusaran, M. & Davies, O.R. (2021) A molecular mechanism for LINC complex branching by structurally diverse SUN-KASH 6:6 assemblies. eLife, 10, e60175. https://doi.org/10.7554/eLife.60175
2020
Sánchez-Sáez, F., Gómez-H, L., Dunne, O.M., Gallego-Páramo, C., Felipe-Medina, N., Sánchez-Martín, M., Llano, E., Pendas, A.M. & Davies, O.R. (2020) Meiotic chromosome synapsis depends on multivalent SYCE1-SIX6OS1 interactions that are disrupted in cases of human infertility. Science Advances, 6 (36), eabb1660. https://doi.org/10.1126/sciadv.abb1660
Sánchez Rodríguez, F., Simpkin, A.J., Davies, O.R., Keegan, R.M. & Rigden, D.J. (2020) Helical ensembles outperform ideal helices in molecular replacement. Acta Crystallographica, D76, 962-970. https://doi.org/10.1107/S205979832001133X
Zhang, J., Gurusaran, M., Fujiwara, Y., Zhang, K., Echbarthi, M., Vorontsov, E., Guo, R., Pendlebury, D.F., Alam, I., Livera, G., Emmanuelle, M., Wang, P.J., Nandakumar, J., Davies, O.R. & Shibuya, H. (2020) The BRCA2-MEILB2-BRME1 complex governs meiotic recombination and impairs the mitotic BRCA2-RAD51 function in cancer cells. Nature Communications, 11, 2055. https://doi.org/10.1038/s41467-020-15954-x
Thomas, J.M.H., Keegan, R.M., Rigden, D.J. & Davies, O.R. (2020) Extending the scope of coiled-coil crystal structure solution by AMPLE through improved ab initio modelling. Acta Crystallographica, D76, 272-284. https://doi.org/10.1107/S2059798320000443
Prior, C.B., Davies, O.R., Bruce, D. & Pohl, E. (2020) Obtaining tertiary protein structures by the ab-initio interpretation of small angle X-ray scattering data. J. Chemical Theory & Computation, 16, 3, 1985-2001. https://doi.org/10.1021/acs.jctc.9b01010
2019
Lepore, R., Kryshtafovych, A. . . . Davies, O.R. . . . Walton, J.D. & Schwede, T. (2019) Target highlights in CASP13: experimental target structures through the eyes of their authors. Proteins, 87 (12), 1037-1057. https://doi.org/10.1002/prot.25805
Voelkel-Meiman, K., Cheng, S.-Y., Parziale, M., Morehouse, S.J., Feil, A., Davies, O.R., de Muyt, A, Borde, V. & MacQueen, A.J. (2019) Crossover recombination and synapsis are linked by adjacent regions within the N terminus of the Zip1 synaptonemal complex protein. PLoS Genetics, 15 (6), e1008201. https://doi.org/10.1371/journal.pgen.1008201
Dunne, O.M. & Davies, O.R. (2019) A molecular model for self-assembly of the synaptonemal complex protein SYCE3. Journal of Biological Chemistry, 294 (23), 9260-9275. https://doi.org/10.1074/jbc.RA119.008404
Dunne, O.M. & Davies, O.R. (2019) Molecular structure of human synaptonemal complex protein SYCE1. Chromosoma, 28 (3), 223-226. https://doi.org/10.1007/s00412-018-00688-z
Levasseur, M.D., Thomas, C., Davies, O.R., Higgins, J.M.G. & Madgwick, S. (2019) Degron-masking controls cyclin B1:CDK1 activity to prevent cell division errors in oocytes. Developmental Cell, 48, 1-18. https://doi.org/10.1016/j.devcel.2019.01.008
2018
Dunce, J.M., Milburn, A.E., Gurusaran, M., da Cruz, I., Sen, L.T., Benavente, R. & Davies, O.R. (2018) Structural basis of meiotic telomere attachment to the nuclear envelope by MAJIN-TERB2-TERB1. Nature Communications, 9, 5355. https://doi.org/10.1038/s41467-018-07794-7
Dunce, J.M., Dunne, O.M., Ratcliff, M., Millan, C., Madgwick, S., Usόn, I. & Davies, O.R. (2018) Structural basis of meiotic chromosome synapsis through SYCP1 self-assembly. Nature Structural & Molecular Biology, 25, 557-569. https://doi.org/10.1038/s41594-018-0078-9
Yang, Y., Denton, H., Davies, O.R., Smith-Jackson, K., Kerr, H., Herbert, A.P., Barlow, P.N., Pickering, M.C. & Marchbank, K.J. (2018) An Engineered Complement Factor H Construct for Treatment of C3 Glomerulopathy. Journal of the American Society of Nephrology, 29 (6), 1649-1661. https://doi.org/10.1681/ASN.2017091006
2017
Syrjanen, J.S., Heller, I., Candelli, A., Davies, O.R., Peterman, E.J., Wuite, G., Pellegrini, L. (2017) Single-molecule observation of DNA compaction by meiotic protein SYCP3. eLife, 6, e22582. https://doi.org/10.7554/eLife.22582
2016
Gómez-H, L., Felipe-Medina, N., Sánchez-Martín, M., Davies, O.R., Ramos, I., Garcia-Tuñón, I., de Rooij, D., Barbero, J.L., Dereli, I., Tóth, A., Benavente, R., Llano, E., and Pendas, A. (2016) The anonymous C14ORF39/SIX6OS1 is a constituent of the synaptonemal complex essential for mouse fertility. Nature Communications, 7, 13298. https://doi.org/10.1038/ncomms13298
Carroll,B., Maetzel, D., Maddocks, O.D., Otten, G., Ratcliff, M., Smith, G.R., Dunlop, E.A., Passos, J.F., Davies, O.R., Jaenisch, R., Tee, A.R., Sarkar, S., Korolchuk, V.I. (2016) Control of TSC2-Rheb signaling axis by arginine regulates mTORC1 activity. eLife, 5, e11058. https://doi.org/10.7554/eLife.11058
2015
Davies, O.R., Forment, J.V., Sun, M., Belotserkovskaya, R., Coates, J., Galanty, Y., Demir, M., Morton, C., Rzechorzek, N., Jackson, S.P. & Pellegrini, L. (2015) CtIP tetramer assembly is required for DNA-end resection and repair. Nature Structural & Molecular Biology, 22, 150-157. https://doi.org/10.1038/nsmb.2937
2014
Syrjanen, J.S., Pellegrini, L. & Davies, O.R. (2014) A molecular model for the role of SYCP3 in meiotic chromosome organisation. eLife, 3, e02963. https://doi.org/10.7554/eLife.02963
2013
Davies, O.R., Lin, C.-Y., Radzisheuskaya, A., Zhou, X., Taube, J., Blin, G., Waterhouse, A., Smith, A.J.H. & Lowell, S. (2013) Tcf15 primes pluripotent cells for differentiation. Cell Reports, 3, 472-484. https://doi.org/10.1016/j.celrep.2013.01.017
2012
Davies, O.R., Maman, J.D. & Pellegrini, L. (2012) Structural analysis of the SYCE2-TEX12 complex provides molecular insights into synaptonemal complex assembly. Open Biology, 2, 120099. https://doi.org/10.1098/rsob.120099
2010
D’Arcy, S., Davies, O.R., Blundell, T.L. & Bolanos-Garcia, V.M. (2010) Defining the molecular basis of BubR1 kinetochore recruitment and APC/C-Cdc20 inhibition. Journal of Biological Chemistry, 285, 19, 14764-76. https://doi.org/10.1074/jbc.M109.082016
2008
Li, Y., Chirgadze, D.Y., Bolanos-Garcia, V.M., Sibanda, B.L., Davies, O.R., Ahnesorg, P., Jackson, S.P. & Blundell, T.L. (2008) Crystal structure of human XLF/Cernunnos reveals unexpected differences from XRCC4 with implications for NHEJ. EMBO Journal, 27, 1, 290-300. https://doi.org/10.1038/sj.emboj.7601942
2007
Davies, O.R. & Pellegrini, L. (2007) Interaction with the BRCA2 C terminus protects RAD51-DNA filaments from disassembly by BRC repeats. Nature Structural & Molecular Biology, 14, 6, 475-483. https://doi.org/10.1038/nsmb1251
2006
Shivji, M.K.K.*, Davies, O.R.*, Savill, J.M., Bates, D.L., Pellegrini, L. & Venkitaraman, A.R. (2006) A region of human BRCA2 containing multiple BRC repeats promotes RAD51-mediated strand exchange. Nucleic Acids Research, 34, 14, 4000-4011. https://doi.org/10.1093/nar/gkl505
Bolanos-Garcia, V.M. & Davies, O.R. (2006) Structural analysis and classification of native proteins from E. coli commonly co-purified by immobilised metal affinity chromatography. Biochimica et Biophysica Acta (Gen), 1760, 9, 1304-1313. Review Article. https://doi.org/10.1016/j.bbagen.2006.03.027
Doré, A.S., Furnham, N., Davies, O.R., Sibanda, B.L., Chirgadze, D.Y., Jackson, S.P., Pellegrini, L. & Blundell, T.L. (2006) The Xrcc4-DNA ligase IV yeast ortholog complex reveals a novel BRCT interaction mode. DNA Repair, 5, 3, 362-368. https://doi.org/10.1016/j.dnarep.2005.11.004
Blundell, T.L., Sibanda, B.L., Montalvao, R.W., Brewerton, S., Chelliah, V., Worth, C.L., Harmer, N.J., Davies, O.R. & Burke, D. (2006) Structural biology and bioinformatics in drug design: opportunities and challenges for target identification and lead discovery. Philos Trans R Soc Lond B Biol Sci, 361, 1467, 413-23. Review Article. https://doi.org/10.1098/rstb.2005.1800