Claire Wyman received her PhD in Molecular Biology from The University of California at Berkeley in 1990 in the
group of Dr. E. Blackburn, where she studied transposons and transposition events involved in the developmental genome rearrangements of Tetrahymena thermophila.  Her postdoctoral work in the laboratory of Dr. H. Echols at the University of California at Berkeley focused on determining the structure of complex nucleoprotein assemblies of DNA replication primarily using electron microscopy to directly visualize such complexes formed in vitro with purified components.  During this time she initiated a collaboration with Dr. Carols Bustamante at the University of Oregon to apply the newly developed technique of Scanning Force Microscopy (SFM) to study DNA replication and transcription mechanisms.

She moved to Rotterdam to join the Department of Cell Biology and Genetics at the Erasmus Medical Center as a research scientist in 1996.  In Rotterdam she set up the Center for Scanning Force Microscopy of Biological Nanomancines to study the molecular machinery involved in DNA repair.  The center has now become a core facility for the NCI (USA) Integrated Project ‘Structural Cell Biology of DNA Repair Machines’.  In addition she established collaborative projects with Dutch biophysics groups to develop and apply new microscopy and single molecule analysis techniques to the study of DNA repair mechanisms.  This work has lead to new understanding of several important functional assemblies of DNA repair machinery and their mechanism of action.  As of 2005 she is an associate professor in the Department of Radiation Oncology at the Erasmus MC and continues to apply SFM as well as novel microscopy and molecular manipulation techniques to advance our understanding of complex mechanisms of genome metabolism. In 2006 she received a VICI award from the Chemical Sciences division of NWO (Netherlands Organization for Scientific Research) to expand this work in new directions.  She is a Course Director for year 1.3 of the Master of Science program in Molecular Medicine at Erasmus MC. In 2008 she was appointed professor of Molecular Radiation Biology.

 

Research summary


My research is aimed at understanding the molecular mechanisms of genome maintenance via homologous recombination repair of DNA double strand breaks. In this post-genomics era we endeavor to understand how essential gene products actually carry out their work. We follow molecular mechanisms by determining the architectural arrangement of multi-protein complexes and by quantitative analysis of their dynamic rearrangements that accompany activity. For this analysis we apply and develop state-of-the-art methods for single-molecule/complex analysis, such as scanning force microscopy (SFM also known as atomic force microscopy or AFM), and TIRF microscopy.  Our active collaborations with Biophysicists (TUD/Dekker, VU Wuite/Peterman) allow us to participate in developing and applying unique and novel single molecule manipulation methods. With these tools we can define the architectural arrangements of functional DNA repair complexes with nm resolution and their dynamic rearrangements in solution in real time.  This work is expanding to increasingly complex machineries to explore the vital molecular mechanisms allowing recombination to occur in chromatin and connecting it to other processes on genome maintenance, such as replication and cell cycle check points.


Key words: Homologous recombination, DNA double-strand break repair, scanning force microscopy, atomic force microscopy and single molecule dynamics

 

Publications


1.  Wyman, C., and E.H.Blackburn. (1991) Tel-1 transposon-like elements of Tetrahymena thermophila are associated with micronuclear genome rearrangements. Genetics 128, p.57-67.


2.  Wyman, C., C. Vasilikiotis, D. Ang, C. Georgopolous, and H. Echols. (1993) Function of the GrpE heat shock protein in bidirectional unwinding and replication from the origin of phage . J. Biol. Chem. 268, p.25192-25199.


3. Wyman, C., E. Grotkopp, C. Bustamante, and H. Nelson. (1995) Determination of heat-shock transcription factor 2 stoichiometry at looped DNA complexes using scanning force microscopy. EMBO J. 14, p.117-123.


4.  Wyman, C., and M. Botchan. (1995) A familiar ring to DNA polymerase processivity.  Current Biology 5, p.334-337.



5. Wyman, C., I. Rombel, A. North, C. Bustamante, and S. Kustu. (1997) Unusual oligomerization required for activity of NtrC, a bacterial enhancer-binding protein. Science 275, p.1658-1661.


7. Van Noort, S.J.T., K.O. van der Werf, A.P.M. Eker, C. Wyman, B.G. de Grooth, N.R. van Hulst and J. Greve. (1998) Direct visualization of dynamic protein-DNA interactions with a dedicated atomic force microscope.  Biophysical J. 74, p.2840-2849.


8. Van Noort, S.J.T., F. Orsini, A. Eker, C. Wyman, B.G. de Grooth and J. Greve.  (1999) DNA bending by photolyase in specific and non-specific complexes studied by atomic force microscopy. Nucleic Acids Res. 27, p.3875-3880.


9. Fortunati, E., E. Ehlert, N-D. van Loo, C. Wyman, J.A. Eble, F. Grosveld and B.J. Scholte. (2000) A multi-domain protein for Beta1 integrin-targeted DNA delivery. Gene Therapy 7, p. 1505-1515


10. Dame, R.T., C.Wyman and N.Goosen. (2000) H-NS mediated compaction of DNA visualized by atomic force microscopy. Nucleic Acids Res. 28, p.3504-3510.


11. Verhoeven, E.E.A., C. Wyman, G.F. Moolenaar, J.H.J. Hoeijmakers and N. Goosen. (2001) The DNA is wrapped around UvrB protein during nucleotide excision repair.  EMBO J. 20, p.601-611.


12. Dame, R.T., C. Wyman and N. Goosen. (2001) Structural basis for preferential binding of H-NS to curved DNA.  Biochimie 83, p. 231-234.


13. Ristic*, D., C. Wyman*, C. Paulusma and R. Kanaar. (2001) The architecture of the human Rad54-DNA complex provides evidence for protein translocation along DNA. Proc. Natl. Acad. Sci. USA 98, p.8454-8460. * equal contribution.


14. De Jager, M., J. van Noort, D.C. van Gent, C. Dekker, R. Kanaar, and C. Wyman. (2001) Human Rad50/Mre11 is a flexible complex that can tether DNA ends. Molecular Cell 8, p. 1129-1135.


15. Dame, R.T., C. Wyman, R. Wurm, R. Wagner, and N. Goosen. (2001) Structural basis for H-NS mediated trapping of RNA polymerase in the open initiation complex at the rrnB P1.  J. Biol. Chem. 277, p. 2146-2150.


16. Dame, R.T., C. Wyman and N. Goosen. (2002) Analysis of transcription and its regulation by scanning force microscopy. In, Science, Technology and Education of Microscopy: An Overview. A. Mendez-Vilas Ed., Formatex.


17. Wyman, C. and R. Kanaar. (2002) Organizing Chromosomes: Reaching out to embrace new models. Current Biology 12, p. 446-448.


18. Verhoeven, E.E.A., C. Wyman, G.F. Moolenaar and N. Goosen. (2002) The presence of two UvrB subunits in the UvrAB complex ensures damage detection in both DNA strands. EMBO J. 21, p.4196-4205.


19. De Jager, M., C. Wyman, D.C. van Gent, R. Kanaar. (2002) DNA end-binding specificity of human Rad50/Mre11 is influenced by ATP. Nucleic Acids Res. 30, p. 4425-4431.


20. Segers-Nolten, G.M.J., C. Wyman, N. Wijgers, W. Vermeulen, A.T.M. Lenferink, J.H.J. Hoeijmakers, J. Greve and C. Otto. (2002) A single molecule study of nucleotide excision repair complexes. Nucleic Acids Res. 30, p. 4720-4727.


21. Essers, J., R.W. Hendriks, J. Wesoly, C.E.M.T. Beerens, B. Smit, J.H.J. Hoeijmakers, C. Wyman, M.L.G. Donkert, and R. Kanaar.  (2002) Cell cycle regulated expression of mouse Rad54 and its implications for homologous recombination.  DNA Repair 2, p. 1-15.


22. Janicijevic, A., K. Sugasawa, N. Wijgers, M. Djurica, J.H.J. Hoeijmakers, and C. Wyman. (2003) Architecture of the human XPC-HR23B DNA complex: damage recognition involves bending DNA. DNA Repair 2, p.325-336.


24. Leliveld, S.R., R. T. Dame, M. A. Mommaas, H. K. Koerten, C. Wyman, A. A. A. M. Danen-van Oorschot, J. L. Rohn, M, H. M. Noteborn, J-P. Abrahams. (2003) Apoptin protein multimers form distinct higher-order nucleoprotein complexes with DNA. Nucleic Acids Res. 31, p. 4805-4813.


25. Tan, T.L.R., R. Kanaar and C. Wyman. (2003) Rad54, a Jack of all trades in homologous recombination.  DNA Repair 2, p. 787-794.


26. van Noort, J., T. van der Heijden, M. de Jager, C. Wyman, R. Kanaar, and C. Dekker. (2003) The coiled-coil of the human Rad50 DNA repair protein contains specific segments of increased flexibility. Proc. Natl. Acad. Sci. USA 100, p.7581-7586. Cover Illustration.


27. Ristic, D., M. Modesti, R. Kanaar and C. Wyman. (2003) Rad52 and Ku bind to different DNA structures produced early in double-strand break repair. Nucleic Acids Res. 31, p.5229-5237.


28. Dame, R.T., C. Wyman, N. Goosen. (2003) Insights into the regulation of transcription by scanning force microscopy. J. Microscopy 212, p. 244-253.


29. Janicijevic, A., D. Ristic and C. Wyman. (2003) The molecular machines of DNA repair: Scanning force microscopy analysis of their architecture. J. Microscopy 212, p. 264-272.


30. Mysiak, M.E., M.H. Bleijenberg, C. Wyman, P.E. Holthuizen and P.C. van der Vliet. (2004) Bending of Adenovirus origin DNA by nuclear factor I as shown by scanning force microscopy is required for optimal DNA replication.  J. Virology, 78, p. 1928-1935.


31. Wyman, C., D. Ristic and R. Kanaar. (2004) Homologous recombination-mediated double-strand break repair. DNA Repair, 3, p. 827-33.


32. De Jager, M., K.M. Trujillo, P. Sung, K-P. Hopfner, J.P. Carney, J.A. Tainer, J.C. Connelly, D.R.F. Leach, R. Kanaar, and C. Wyman. (2004) Differential arrangements of conserved building blocks among homologs of the SMC family member and DNA repair protein Rad50/Mre11, J.  Molec. Biol. 339, p. 937-949. Cover illustration.


33. Wyman, C., R. Kanaar R. (2004) Homologous recombination: down to the wire. Current Biology 14, R629-631.


34. Lansbergen G., Y. Komarova , M. Modesti , C. Wyman , C. C. Hoogenraad , H. V. Goodson , F. Grosveld, N. Galjart , G. G. Borisy and A. Akhmanova (2004) Conformational changes in CLIP-170 regulate its binding to microtubules and dynactin localization. J.  Cell Biology 166, p. 1003-1014. Cover illustration.


35. Mysiak, M.E., C. Wyman, P.E. Holthuizen, and P.C. van der Vliet. (2004) NFI and Oct-1 bend the Ad5 origin in the same direction leading the optimal DNA replication. Nucleic Acids Res. 32, p.6218-6225.


36. Beerens, N., J.H.J. Hoeijmakers, R. Kanaar, W. Vermeulen, and C. Wyman. (2005) The CSB protein actively wraps DNA. J. Biol. Chem. 280, p. 4722-4729.


37. Essers, J., W.A. van Cappellen, A.F. Theil, E . van Drunen, N.G. Jaspers, J.H. Hoeijmakers, C. Wyman, W. Vermeulen, and R. Kanaar. (2005)  Dynamics of Relative Chromosome Position during the Cell Cycle.  Mol. Biol. Cell. 16, p. 769-775.


38. Schlacher, K., K. Leslie, C. Wyman, R. Woodgate, M. Cox, and M.F. Goodman. (2005) DNA polymerase V and RecA protein, a minimal mutasome.  Molecular Cell, 17, p. 561-572.


39. van der Heijden, T., J. van Noort, H. van Leest, R. Kanaar, C. Wyman, N. Dekker and C. Dekker (2005) Torque-limited RecA polymerization on dsDNA.  Nucleic Acids Res. 33, p. 2099-2105.


40. Dame, R.T., J. van Mameren, G. M.S. Luisterburg, M.E. Mysiak, A. Janicijevic, G. Pazdzior, P.c. van der Vliet, C. Wyman and J.L. Wuite (2005) Simulation-based estimation of protein-induced DNA binding angles by scanning force microscopy. Nucleic Acids Res. 33, e68, doi:10.1093/nar/gni073


41. Ristic, D., M. Modesti, T. van der Heijden, J. van Noort, C. Dekker, R. Kanaar and C. Wyman (2005) Human Rad51 filaments on double- and single-stranded DNA: Correlating regular and irregular forms with recombination function. Nucleic Acids Res. 33, p. 3292-3302, doi:10.1093/nar/gki640.


42. Ciferri, C., J. De Luca, S. Monzani, K. Ferrari, D. Ristic, C. Wyman, H. Stark, J. Kilmartin, E.D. Salmon and A. Musacchio (2005) Architecture of the human Hec1/Ndc80 complex, a critical constituent of the outer kinetochore.  J. Biol. Chem. 280, p. 29088-2909.


43. Moreno-Herrero,F., M. de Jager, N.H. Dekker, R. Kanaar, C. Wyman*and C. Dekker* (2005) Mesoscale conformational changes in the DNA-repair complex Rad50/Mre11/Nbs1 upon DNA binding. Nature 473, p. 440-443, doi:10.1038/nature03927. * corresponding author


44. Wyman C. (2006) Balancing Responsibilities. EMBO Reports 7, p. 2.


45. Wyman, C. (2006) Monomer networking activates recombinases. Structure 14, p. 949-951.


47. van Mameren, J., M. Modesti, R. Kanaar, C. Wyman, G. J. L. Wuite, and E. J. G. Peterman (2006) Dissecting elastic heterogeneity along DNA molecules coated partly with Rad51 using concurrent fluorescence microscopy and optical tweezers. Biophys. J. 91, p. L78-80.


48. Eppink, B., C. Wyman and R. Kanaar (2006) Multiple interlinked mechanisms to circumvent DNA replication roadblocks. Expt. Cell Res. 312, p. 2660-2665.


49. Wyman, C., and R. Kanaar (2006) DNA double-strand break repair: All’s well that ends well.  Ann. Rev. Genetics, 40, p. 363-83


50. Hanada, K., J. Essers, M. Budzowska, M. Modesti, A. Maas, C. Wyman, and R. Kanaar (2006) The structure-specific endonuclease Mus81-Eme1 promotes conversion of interstrand DNA cross-links into double-strand breaks. EMBO J. 25, p.4921-32.


51. Mohd-Sarip, A., J.A. van der Knaap, C. Wyman, Roland Kanaar, P. Schedl and C.P. Verrijzer (2006) Architecture of a Polycomb Nucleoprotein Complex. Molecular Cell 24, p. 91-100. cover illustration


52. Van der Heijden T, F. Moreno-Herrero, R. Kanaar, C. Wyman, and C. Dekker (2006) Comment on "Direct and Real-Time Visualization of the Disassembly of a Single RecA-DNA-ATPγS Complex Using AFM Imaging in Fluid". Nano Letters 6, p. 3000-3002


53. Van der Heijden T, F. Moreno-Herrero, R. Kanaar, C. Wyman, and C. Dekker (2007) AFM Tip-Induced Dissociation of RecA-dsDNA Filaments. Nano Letters 7, p. 1112.


54. Seeling, J., K. Leslie, A. Renn, S. Kuhn, V. Jacobsen, M. van de Corupt, C. Wyman and V. Sandoghdar. (2007) Nanoparticle Induced Fluorescence Lifetime Modification as Nanoscopis Ruler: Demonstration at the Single Molecule Level. Nano Letters  vol. 7, p. 685-689.


55.  Modesti, M., D., Ristic, T. van der Heijden, C. Dekker, J. van Mameren, E.J. Peterma, G.J. Wuite, R. Kanaar, and C. Wyman. (2007) Fluorescent Human RAD51 Reveals Multiple Nucleation Sites and Filament Segments Tightly Associated along a Single DNA Molecule. Structure 15, p. 599-609.


  1. 56.van der Heijden, T., R. Seidel, M. Modesti, R. Kanaar , C. Wyman*, and C. Dekker*. (2007) Real-time assembly and disassembly of human RAD51 filaments on individual DNA molecules. Nucleic Acids Res. Aug 20 (epub ahead of print) * corresponding author

  2. 57.Kanaar, R., Wyman, C. and Rothstein, R.  (2008).  Quality control in DNA break metabolism:  In the ‘end’, it’s a good thing.  EMBO J. 27, 581-588.


  1. 58.Wyman, C., Warmerdam, D.O. and Kanaar, R.  (2008).  From DNA end chemistry to cell-cycle response:  The importance of structure, even when it’s broken. Mol. Cell 30,  5-6.

  2. 59.Van der Heijden, T., Modesti, M., Hage, S., Kanaar, R., Wyman, C., Dekker, C.  (2008).  Homologous recombination in real time: DNA strand exchange by RecA.  Mol. Cell 30, 530-538.

  3. 60.Kanaar, R. and Wyman, C.  (2008).  DNA repair by the MRN complex:  Break it to make it.  Cell, in press.

  4. 61.van Mameren, J., Modesti, M., Kanaar, R., Wyman, C., Peterman, E. J. and Wuite, G. J.  (2008).  Counting RAD51 proteins disassembling from nucleoprotein filaments under tension.  Nature, in press.


Contact details


Room Ee 669a

Phone: +31 10 704 4337

Fax: +31 10 704 4747

Email: c.wyman@erasmusmc.nl

Home page: http://web.mac.com/carolwymanmac