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Lebbink, Joyce

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Dr.ir. Joyce LebbinkJoyce Lebbink studied Molecular Sciences (specialty Biochemistry) at Wageningen University, the Netherlands. 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 as a 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 (MMR). Since September 2007 she is further studying MMR and its interactions with Homologous Recombination as Assistant Professor in the Molecular Radiation Biology group at Erasmus Medical Center.

Joyce was coordinator of the European consortium ’mismatch2model’, and has received Marie Curie, VENI and VIDI personal fellowships.

Current research interests:

DNA mismatch repair (MMR) corrects DNA replication errors and inhibits recombination between DNA with diverging sequences. Bacteria and eukaryotes without functional mismatch repair develop mutator phenotypes. In higher eukaryotes 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 the mechanistic details of mismatch recognition, repair complex formation, activation of the different repair enzymes and ultimately, correct mismatch repair or abortion of the recombination event.

Address

Erasmus MC - Dept of Genetics
room Ee 06-69
PO Box 2040
3000 CA Rotterdam
The Netherlands

Phone+31-10-703 0473
Emailj.lebbink - at - erasmusmc.nl
Webpage http://www.erasmusmc.nl/genetica/research/MRBhome

Selected Publications:

Tham KC, Hermans N, Winterwerp HHK, Cox MC, Wyman C, Kanaar R and Lebbink JHG. Mismatch Repair Inhibits Homeologous Recombination via Coordinated Directional Unwinding of Trapped DNA Structures. Mol. Cell. 51, 326-337, 2013.

Groothuizen FS, Fish A, Petoukhov MV, Reumer A, Manelyte L, Winterwerp HHK, Marinus MG, Lebbink JHG, Svergun DI, Friedhoff P and Sixma TK. Using stable MutS dimers and tetramers to quantitatively analyze DNA mismatch recognition and sliding clamp formation. Nucleic Acids Res. 14, 8166-8181, 2013.

Xiao Y, Jung C, Marx AD, Winkler I, Wyman C, Lebbink JHG, Friedhoff P, Cristovao M. Generation of DNA nano-circles containing mismatched bases. Biotechniques 51, 259-265, 2011.

Wyman C, Lebbink JHG, Kanaar R (2011) Mre11-Rad50 complex crystals suggest molecular calisthenics. DNA Repair 10:1066-1070

Monti MC, Cohen SX, Fish A, Winterwerp HHK, Barendregt A, Friedhoff P, Perrakis A, Heck AJR, Sixma TK, van den Heuvel RHH and Lebbink JHG (2011) Native mass spectrometry provides direct evidence for DNA mismatch induced regulation of asymmetric nucleotide binding in mismatch repair protein MutS. Nucleic Acids Res 39:8052-8064

Lebbink JHG, Fish A, Reumer A, Natrajan G, Winterwerp HHK, Sixma TK (2010) Magnesium coordination controls the molecular switch function of DNA mismatch repair protein MutS. J Biol Chem 285:13131-13141

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