Role of SPRTN in resolution of DNA protein crosslinks and replication stress (08)

• Subject Area: General Genetics and Functional Genome Biology
• Term: since 2019
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 393547839

DNA-protein crosslinks (DPCs) are one of the most severe forms of DNA damage. Yet, little is known about mechanisms of repairing DPCs. In this project we focus on the Sprt-type proteases that resolve DPCs to overcome replication stress and faithfully repair the lesions. In humans, SPRTN germline mutations result in Ruijs-Aalfs syndrome, characterised by segmental progeria with early onset of hepatocellular carcinoma. We will investigate how dysregulation of the innate immune system in Sprt-mutated cells contributes to the age-ing process and cancer development in the liver. Taken together, this project will provide molecular and ge-netic insights into the intrinsic molecular mechanisms that resolve DPCs and prevent ageing and cancer.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1361: Regulation of DNA Repair and Genome Stability
• Applicant Institution: Johannes Gutenberg-Universität Mainz
• Project Head: Professor Dr. Ivan Dikic