Molecular mechanisms of DNA damage-induced cell fate decisions (03)

• Subject Area: Cell Biology
• Term: from 2012 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 201348542

The group of Thomas Hofmann (TP03) examines signaling pathways that determine cell fate upon DNA damage, focusing on the kinases ATM and HIPK2. The group identified a conserved mechanism of HIPK2 activation upon DNA damage involving autophosphorylation and Pin1-mediated isomerization of the kinase. In addition, the group identified the Sirtuin deacetylase SIRT1 as a HIPK2 substrate and demonstrated that SIRT1 phosphorylation upon DNA damage inhibits its deacetylase activity, enables efficient p53 acetylation and thereby promotes expression of pro-apopototic p53 target genes. In the second funding period we plan to decipher the role of a HIPK2- and p53-interacting adaptor protein in cell fate control upon DNA damage as well as the role of HIPK2 in DNA repair.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1036: Cellular Surveillance and Damage Response
• Applicant Institution: Ruprecht-Karls-Universität Heidelberg
• Co-Applicant Institution: Deutsches Krebsforschungszentrum (DKFZ)
• Project Head: Professor Dr. Thomas G. Hofmann, Ph.D.