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SFB 1361:  Regulation of DNA Repair and Genome Stability

Subject Area Biology
Medicine
Term since 2019
Website Homepage
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 393547839
 
Quality control systems that safeguard cellular integrity are essential for life. DNA repair and damage re-sponse pathways rank among the cell’s principal surveillance systems as they ensure not only the safe stor-age and accurate transmission of its genetic information, but also the correct translation of the genetic code to produce the structural and enzymatic components of the cell. Beyond their protective functions, DNA repair systems contribute to a variety of regulatory processes, such as the control of gene expression via epigenetic DNA modifications or the generation of diversity in the immune system. Consequently, deficien-cies in genome maintenance result in a variety of disorders, ranging from various malignancies to immuno-logical and neurological disorders and accelerated ageing. Understanding how DNA repair and damage sig-nalling are regulated is therefore key to our efforts to promote human health.The objective of the CRC 1361 is to elucidate the regulatory mechanisms governing the choice between individual genome maintenance pathways, their fidelity, their interdependencies and their contributions to cellular physiology. During its first funding period, the CRC has made critical advances in characterising components of DNA repair and damage signalling systems as decision-makers in the regulation of genome maintenance. In particular, our research has highlighted the relevance of endogenous factors as sources of genome instability. In the next funding period, the CRC aims to deepen its mechanistic analysis of genome maintenance systems and intensify efforts to draw functional connections between individual repair path-ways to integrate them into larger regulatory networks. This will require enhanced systems-level approaches to identify expanded protein-DNA and protein-protein interaction networks and to determine the genome-wide distribution of lesions to gain an understanding of their implications in a larger context. The CRC’s dedi-cated service platforms in Quantitative Proteomics and Genomics & Bioinformatics have been essential col-laboration partners in the development of this technology and will continue to act as critical supporting struc-tures for the planned research. With their contributions, we will focus our investigation primarily on the vari-ous endogenous sources of genome instability, their perception by cellular signalling pathways, their processing by dedicated or overlapping DNA repair pathways and their implications for cell fate and physiology. The interdisciplinary nature of the CRC, spanning structural and molecular biology, biochemistry, genetics and genomics, cell biology, toxicology and computational biology, will contribute to the consolidation of Mainz as a hub of genome stability research and ensure a high-quality education for the next generation of scientists in the field.
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