Single molecule studies of the interplay between DNA repair mechanisms and between DNA repair and DNA replication and transcription

• Applicant: Ingrid Teßmer, Ph.D.
• Subject Area: Biophysics ; Biochemistry
• Term: since 2022
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 508046170

The stability of DNA is constantly chemically and physically threatened, resulting in structurally altered or chemically modified DNA that can lead to cancer, cell senescence, or apoptosis. Different DNA modifications are repaired by a number of DNA repair mechanisms that are fine-tuned to their particular target lesions. Several recent studies have also pointed at interactions between different DNA repair systems as well as between DNA repair and DNA transcription and replication. We plan to investigate the interplay of direct damage reversal DNA alkyltransferases and base excision repair (BER) glycosylases with proteins from the nucleotide excision repair (NER) system. Initiation of NER by alkyltransferases and glycosylases may be achieved via stalling of transcription or direct protein-protein interactions in transcription-coupled NER or global genome NER, respectively. Alkyltransferases have also been shown to interact with proteins involved in the initiation of DNA replication. Our single molecule imaging approaches using atomic force microscopy (AFM) and fluorescence optical tweezers, combined with on the one hand ensemble biophysical and functional biochemical assays and on the other hand crystallisation studies aim to provide mechanistic insight into the interactions between these fundamentally important DNA processing systems.

• DFG Programme: Research Grants