My Research

Puck Knipscheer has been interested in understanding the molecular details of biological processes since her PhD (2007) at the Netherlands Cancer Institute with Prof. Titia Sixma. Here she used X-ray crystallography and biochemistry to investigate posttranslational modification by the ubiquitin-like modifier SUMO. During her postdoc in the laboratory of Johannes Walter at Harvard Medical School she started to study genome maintenance.

She contributed to the development of a unique Xenopus egg extract based system that allows the repair of highly toxic DNA interstrand crosslinks (ICLs) under physiological conditions in vitro. Subsequently, she used this system to elucidate the role of the Fanconi anemia protein FANCD2 and showed for the first time how the activated Fanconi anemia pathway acts in a specific step in ICL repair.

In 2011 she started her own laboratory at the Hubrecht Institute in Utrecht where she continued her investigations into this poorly understood DNA repair pathway. She identified the long sought endonuclease that unhooks an ICL during repair. In addition, she developed a system to study G4 structure unwinding under physiologically relevant conditions and found a direct role for the helicase FANCJ. She currently continues to use this system to investigate the mechanisms by which stable secondary DNA structures are resolved during DNA replication.

Awards

• 2010: Heineken Young Scientist Award for Biochemistry and Biophysics, Royal Netherlands Academy of Arts and Sciences (KNAW)

Key Publications

1. Bosch, P. C., Segura‐Bayona, S., Koole, W., van Heteren, J. T., Dewar, J. M., Tijsterman, M., & Knipscheer, P. (2014). FANCJ promotes DNA synthesis through G‐quadruplex structures. The EMBO journal, e201488663.
2. Douwel, D. K., Boonen, R. A., Long, D. T., Szypowska, A. A., Räschle, M., Walter, J. C., & Knipscheer, P. (2014). XPF-ERCC1 acts in Unhooking DNA interstrand crosslinks in cooperation with FANCD2 and FANCP/SLX4. Molecular cell, 54(3), 460-471.
3. Douwel, D. K., Hoogenboom, W. S., Boonen, R. A., & Knipscheer, P. (2017). Recruitment and positioning determine the specific role of the XPF‐ERCC1 endonuclease in interstrand crosslink repair. The EMBO journal, 36(14), 2034-2046.
4. Knipscheer, P., Räschle, M., Smogorzewska, A., Enoiu, M., Schärer, O. D., Elledge, S. J., & Walter, J. C. (2009). The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science, 326(5960), 1698-1701.
5. Räschle, M., Knipscheer, P., Enoiu, M., Angelov, T., Sun, J., Griffith, J. D., ... & Walter, J. C. (2008). Mechanism of replication-coupled DNA interstrand crosslink repair. Cell, 134(6), 969-980.