Personal Fellowships:

• NWO-VENI grant ‘Structural and Functional Characterization of DNA Mismatch Repair Protein Complexes’.

• EMBO long-term fellowship ‘X-ray structure analysis of Pullulanases from Hyperthermophilic Archaea and Bacteria’, Fellowship awarded but not used.

1. •Marie Curie Individual Fellowship ‘X-ray structure analysis of Pullulanases from Hyperthermophilic Archaea and Bacteria’.
   

2. •NWO-VIDI grant ‘Recombination meets its mismatch: A structural and mechanistic analysis of antirecombination by the DNA mismatch repair machinery.’
   

Joyce Lebbink

Dr. Ir. Joyce H.G. Lebbink was born on October 6, 1969. She studied Molecular Sciences (specialty Biochemistry) at the Wageningen University and Research Center in the Netherlands from 1988 to 1994. She obtained her PhD in 1999 at the same University, characterizing molecular details of thermostable enzymes at the Department of Microbiology. She further obtained experience in biophysics and structural biology during her Postdoc at the Center for Structural Biochemistry, Karolinska Institute in Sweden. In 2002 she returned to the Netherlands as Postdoc in the Protein Crystallography group of Prof. Titia Sixma at the Netherlands Cancer Institute to study structure and mechanisms of DNA Mismatch Repair. Since September 2007 she is further studying MMR and its interactions with Homologous Recombination at the Molecular Radiation Biology group at the Erasmus Medical Center.

Research interest

DNA mismatch repair (MMR) corrects DNA replication errors and inhibits recombination between DNA with diverging sequences. In both bacteria and eukaryotes, the loss of mismatch repair gives rise to a mutator phenotype. In the most frequent form of familiar cancer, HNPCC (hereditary non-polyposis colon cancer), germline mutations in one of the DNA mismatch repair genes predispose to cancer of the colon, endometrium, ovary and other organs.

We would like to understand in mechanistic detail how the recognition of a DNA mismatch during DNA replication or in recombination intermediates results in intramolecular signaling, repairosome complex formation and ultimately, correct mismatch repair or abortion of the recombination event.

Contact details

Joyce Lebbink

Phone + 31 (0) 10 704 3604

Fax +31 (0) 10 704 4747

Email: j.lebbink@erasmusmc.nl

Publications

Cohen SX, Jelloul MB, Long F, Vagin A, Knipscheer P, Lebbink JH, Sixma TK, Lamzin VS, Murshudov GN and Perrakis A. ARP/wARP and molecular replacement: the next generation. Acta Cryst D 64, 49–60, 2008.

Lebbink JH, Georgijevic D, Natrajan G, Fish A, Winterwerp HH, Sixma TK, de Wind N. Dual role of MutS glutamate 38 in DNA mismatch discrimination and in the authorization of repair. EMBO J 25, 409-419, 2006.

Romier C, Jelloul MB, Albeck S, Buchwald G, Busso D, Celie PHN, Christodoulou E, De Marco V, van Gerwen S, Knipscheer P, Lebbink JH, Notenboom V, Poterszman A, Rochel N, Cohen SX, Unger T , Sussman JL, Moras D, Sixma TK, Perrakis A. Co-expression of protein complexes in prokaryotic and eukaryotic hosts: experimental procedures, database tracking and case studies. Acta Cryst D 62, 1232-1242, 2006.

Lebbink JH, Sixma TK. Variations on the ABC. Structure 13, 498-500, 2005.

Lamers MH, Georgijevic D, Lebbink JH, Winterwerp HH, Agianian B, de Wind N, Sixma TK. ATP increases the affinity between MutS ATPase domains: Implications for ATP hydrolysis and conformational changes. J Biol Chem 279, 43879-85, 2004.

Lebbink JHG, Consalvi V, Chiaraluce R, Berndt KD, Ladenstein R. Structural and thermodynamic studies on a salt-bridge triad in the NADP-binding domain of glutamate dehydrogenase from Thermotoga maritima: cooperativity and electrostatic contribution to stability. Biochemistry 41, 15524-15535, 2002.

Chiaraluce R, Oost J van der, Lebbink JHG, Kaper TK, Consalvi V. Persistence of tertiary structure in 7.9 M guanidinium chloride: the case of endo-β-1,3-glucanase from Pyrococus furiosus. Biochemistry 41, 14624-14632, 2002.

Buhler C, Lebbink JHG, Bocs C, Ladenstein R, Forterre P. DNA topoisomerase VI generates ATP dependant double-strand breaks with two-nucleotide overhangs. J Biol Chem 276, 37215-37222, 2001.

Lebbink JHG, Kaper T, Kengen SWM, van der Oost J, de Vos WM. The β-glucosidase CelB from Pyrococcus furiosus: Production in Escherichia coli, purification and in vitro evolution. Meth Enz, Volume ‘Hyperthermophilic enzymes’ 330, 364-79, 2001.

Kaper T, Verhees CH, Lebbink JHG, van Lieshout JFT, Kluskens LD, Ward DE, Kengen SWM, de Vos WM, van der Oost J. Characterization of b-glycosyl hydrolases from Pyrococcus furiosus. Meth Enz, Volume ‘Hyperthermophilic enzymes’ 330, 329-46, 2001.

Lebbink JHG, Kaper T, Bron P, van der Oost J, de Vos WM. Improving low-temperature catalysis in the hyperthermostable Pyrococcus furiosus -glucosidase CelB by directed evolution. Biochemistry 39, 3656-3665, 2000.

Kaper K, Lebbink JHG, Pouwels J, Kopp J, Schulz GE, van der Oost J, de Vos WM. Comparative structural analysis and substrate specificity engineering of the hyperthermostable β-glucosidase from Pyrococcus furiosus. Biochemistry 39, 4963-4970, 2000.

Pouwels J, Moracci M, Cobucci-Ponzano B, Perugino G, van der Oost J, Kaper T, Lebbink JHG, de Vos WM, Ciaramella M, Rossi M. Activity and stability of hyperthermophilic enzymes: a comparative study on two archaeal b-glycosidases. Extremophiles, 2000, 4, 157-64.

Brinkman A, Dahlke I, Tuininga J, Lammers T, Dumay V, de Heus E, Lebbink J, Thomm M, de Vos WM, van der Oost J. An Lrp-like transcriptional regulator from the archaeon Pyrococcus furiosus is negatively autoregulated. J Biol Chem, 275, 38160-9, 2000.

Lebbink JHG, Bertoldo C, Tibbelin G, Andersen JT, Duffner F, Antranikian G, Ladenstein R. Crystallization and preliminary X-ray crystallographic studies of the thermoactive pullulanase type I from Fervidobacterium pennivorans Ven5. Acta Cryst D 56, 1470-1472, 2000.

Lebbink JHG, Knapp S, van der Oost J, Rice D, Ladenstein R, de Vos WM. Engineering activity and stability of Thermotoga maritima glutamate dehydrogenase. II. Construction of a 16-residue ion-pair network at the subunit interface. J Mol Biol 289, 357-369, 1999.

Lebbink JHG, Kengen SWM, van der Oost J, de Vos WM. Glutamate dehydrogenase from hyperthermophilic Bacteria and Archaea: determinants of thermostability and catalysis at extremely high temperatures. J Mol Catal. B, Enzymatic 7, 133-145, 1999.

Yip KS, Britton KL, Stillman TJ, Lebbink J, de Vos WM, Robb FT, Vetriani C, Maeder D, Rice DW. Insights into the molecular basis of thermal stability from the analysis of ion-pair networks in the glutamate dehydrogenase family. Eur J Biochem 255, 336-46, 1998.

Lebbink JHG, Knapp S, van der Oost J, Rice D, Ladenstein R, de Vos WM. Engineering activity and stability of Thermotoga maritima glutamate dehydrogenase. I. Introduction of a six-residue ion-pair network in the hinge region. J Mol Biol 280, 287-96, 1998.

Ramos A, Raven ND, Sharp RJ, Bartolucci S, Rossi M, Cannio R, Lebbink JHG, van der Oost J, de Vos WM, Santos H. Stabilisation of enzymes against thermal stress and freeze-drying by mannosylglycerate. Appl Env Microbiol 63, 4020-4025, 1997.

Lebbink JHG, Eggen RIL, Geerling ACM, Consalvi V, Chiaraluce R, Scandurra R, de Vos WM. Exchange of domains of glutamate dehydrogenase from the hyperthermophilic archaeon Pyrococcus furiosus and the mesophilic bacterium Clostridium difficile: effects on catalysis, thermoactivity and stability. Prot Eng 8, 1287-1294, 1995.