Probing the functions of mammalian Cdk2 in the DNA damage response with chemical genetics

• Antragstellerin: Dr. Lara Wohlbold
• Fachliche Zuordnung: Zellbiologie
• Förderung: Förderung von 2006 bis 2009
• Projektkennung: Deutsche Forschungsgemeinschaft (DFG) - Projektnummer 27337483

The cell division cycle is intimately connected with the response to genotoxic stress. One well studied example of this linkage is the checkpoint pathway that conveys the presence of DNA damage or its ongoing repair to the cell cycle machinery, leading ultimately to cell cycle arrest or apoptosis. However, recent studies in yeast and mammals reveal another connection between the cell cycle and DNA repair: the cyclin-dependent kinases (CDKs)—principal effectors of cell cycle transitions—directly coordinate DNA repair processes with progression through the cell cycle. In both budding and fission yeast, for example, the activity of CDKs directly promotes repair of double strand breaks (DSBs) by homologous recombination (HR) during the G2 phase of the cell cycle when sister chromatids are available 1-3. In mammalian cells it could be shown that inhibition of Cdk2, the major CDK active throughout the cell cycle, results in defects of DNA damage repair by HR and non-homologous end joining (NHEJ)4. Furthermore, Cdk2-knockout mice are sterile due to meiotic defects reminiscent of those seen in mice lacking components of DNA repair machinery5-7. In this study I plan to investigate the role(s) of the cell cycle machinery, specifically Cdk2, in the DNA damage response in human cells using a chemical genetic approach.

• DFG-Verfahren: Forschungsstipendien
• Internationaler Bezug: USA
• Gastgeber: Professor Dr. Robert P. Fisher