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Knipscheer group

Molecular mechanism and regulation of DNA repair

DNA repair mechanisms are crucial to maintain genomic integrity and prevent cancer. A particularly harmful type of DNA damage is an interstrand crosslink (ICL), which covalently links the two strands of the DNA. High doses of ICLs are used in cancer therapy but ICLs are also formed under normal conditions. Surprisingly little is known about the biochemical mechanism of ICL repair and especially the role of the Fanconi anemia pathway has remained enigmatic. Fanconi anemia is a genetic cancer predisposition disorder characterized by hypersensitivity to ICLs. We use Xenopus laevis egg extracts to recapitulate ICL repair in vitro, which allows us to study its molecular mechanism and regulation.

About the research

Fast Facts: A roadblock on the DNA highway from Fast Facts on Vimeo.

Key publications
Pau Castillo Bosch, Sandra Segura-Bayona, Wouter Koole, Jane van Heteren, James Dewar, Marcel Tijsterman# and Puck Knipscheer# (2014). FANCJ promotes DNA synthesis through G-quadruplex structures. EMBO J, September 5th [Epub ahead of print].

Daisy Klein Douwel*, Rick A.C.M. Boonen*, David T. Long, Anna A. Szypowska, Markus Räschle, Johannes C. Walter, and Puck Knipscheer (2014). XPF-ERCC1 acts in unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Mol Cell. 54(3):460-71.

Puck Knipscheer, Markus Räschle, Agata Smogorzewska, Milica Enoiu, The Vinh Ho, Orlando D. Schärer, Stephen J. Elledge, and Johannes C. Walter (2009) The Fanconi anemia pathway promotes replication-dependent DNA interstrand crosslink repair. Science. 326:1698-1701.

Markus Räschle, Puck Knipscheer, Milica Enoiu, Todor Angelov, Jingchuan Sun, Jack D. Griffith, Tom E. Ellenberger, Orlando D. Schärer, and Johannes C. Walter (2008) Mechanism of Replication-Coupled DNA Interstrand Crosslink Repair. Cell. 134:969-980.

Puck Knipscheer*, Annette Flotho*, Helene Klug*, Jesper V Olsen, Willem J van Dijk, Alexander Fish, Erica S. Johnson, Matthias Mann, Titia K Sixma and Andrea Pichler (2008) Ubc9 sumoylation regulates SUMO target discrimination. Mol Cell. 31:371-382.

Publication list