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SFB 646:  Networks in Genome Expression and Maintenance

Subject Area Biology
Term from 2005 to 2016
Project identifier Deutsche Forschungsgemeinschaft (DFG) - Project number 5486242
 
Final Report Year 2019

Final Report Abstract

The Collaborative Research Centre 646 (CRC646) set out to elucidate the molecular mechanisms and processes underlying two central and highly interconnected cellular functions, namely the expression and the maintenance of eukaryotic genomes, with a special emphasis on the physical and functional coupling between such processes. The expression of the genome was the focus of research area A, which comprised studies of RNA transcription, processing, nuclear export, cellular localization, translation, and turnover. In research area B the maintenance of the genome was analyzed, which included studies of DNA packaging, silencing, replication, homologous recombination and repair. A particular focus was on research projects that bridge between these two areas and the individual processes. Over the entire funding period from 2005 to 2016 numerous discoveries were made, often in an increasingly collaborative manner, and novel findings contributed to a new molecular understanding of the above mentioned processes. Already in the early phase of the CRC646, researchers provided for example a molecular description of RNA transcription-dependent DNA damage recognition and a structural framework for the transcription by the RNA polymerase I of genes not coding for proteins, such as ribosomal rDNA. Other examples are the first structure of a DNA remodeling enzyme in complex with its substrate, the description of a yeast complex mediating mRNA localization or the elucidation of the mechanism of ribosome recycling. Later, with new project leaders new technologies and new model organisms, such as the fruitfly D. melanogaster or the nematode worm C. elegans, were introduced to the CRC646. The new technology comprised computational methods, more system-wide approaches for monitoring protein-DNA interplay or RNA metabolism, and high-resolution cryo-electron microscopy. New organisms and new technology set the stage for broader approaches, and the later projects included now the characterization of transcriptional regulatory networks, RNA-mediated heterochromatin formation and gene silencing, and the maintenance of chromatin structure by a histone chaperone. However, also the initial projects developed successfully to provide a mechanistic understanding of transcription coactivator-mediated gene regulation, transcription-coupled mRNA export, the epigenetic role of newly described DNA cytosine modifications, and of translation coupled mRNA decay. These outstanding achievements are characterized by highly collaborative efforts within the CRC646 and their scientific value is underscored by numerous publications in high ranking international journals such as Nature, Cell and Science. Most importantly, of the (difficult to select) 40 most important publications resulting from CRC646 funded projects, one half is co-authored by two or more project leaders of the CRC. As a result, a wealth of entirely novel molecular insights were gained and could often be integrated into a systemwide functional understanding. Taken together, the CRC646 successfully generated synergies and left an exceptionally positive mark not only in the scientific community but also on the growing LMU Munich campus where it is further fostering a fundamentally improved understanding of eukaryotic genome maintenance and gene expression.

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