Objective
DNA double-strand breaks (DSBs) are toxic lesions that must be efficiently repaired to maintain genome integrity. Following DNA damage, cells activate a multi-layered signalling and repair network termed the DSB response. Emerging organizers of this DSB response are various RNAs and RNA-binding proteins, which display characteristic localization dynamics at the damaged-chromatin. The laboratory of Stephanie Panier recently showed that many heterogeneous nuclear ribonucleoproteins (hnRNPs) are actively excluded from damaged chromatin soon after the induction of DSBs. The exact purposes of hnRNP exclusion and the underlying regulatory mechanisms remain to be determined. In my postdoctoral project, I propose to study why and how hnRNPs are excluded from damaged chromatin. To this end, 1) I will characterize the exclusion properties of the hnRNPs at DSBs using cellular models and unique genetic and microscopy approaches. 2) I will also identify protein and RNA complexes associated with hnRNPs at DSB sites using proximity labelling proteomics and RNA-sequencing approaches. In studying these hnRNPs, I will unravel the new mechanisms by which RNAs help to organize the DSB response. The combination of state-of-the-art cell biological and omic approaches will enable me to go well beyond the current knowledge of the field to characterize novel factors and mechanisms that coordinate RNA biology at DSB sites. Since genome instability and defects in RNA metabolism are both directly linked to the pathogenesis of cancer and also neurodegeneration, my findings will have direct implications for human health.
Fields of science (EuroSciVoc)
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
CORDIS classifies projects with EuroSciVoc, a multilingual taxonomy of fields of science, through a semi-automatic process based on NLP techniques.
- natural sciencesbiological sciencesneurobiology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteinsproteomics
- natural sciencesbiological sciencesgeneticsDNA
- medical and health sciencesclinical medicineoncology
- natural sciencesbiological sciencesgeneticsRNA
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Programme(s)
- HORIZON.1.2 - Marie Skłodowska-Curie Actions (MSCA) Main Programme
Funding Scheme
HORIZON-TMA-MSCA-PF-EF - HORIZON TMA MSCA Postdoctoral Fellowships - European FellowshipsCoordinator
80539 Munchen
Germany