Project Details
Projekt
Phase separation in PML nuclear bodies through a multivalent polySUMO-2/3 network is required for efficient DNA recombination and repair
Subject Area
Cell Biology
Biophysics
Biophysics
Term
since 2019
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 419138358
The spatial organization of biochemical activities is an extremely important task for each living cell. Mammalian cells manage this task by concentrating essential cellular functions into membrane-enclosed compartments or into membrane-less organelles. The molecular mechanisms underlying the formation, the maintenance and the function of membrane-less organelles is only now begining to be unraveled. The main physical driver of the assembly of membrane-less organelles is liquid-liquid phase seperation (LLPS) and this mechanism is initiated by a specific class of molecules (Protein, RNA, DNA) with particular biophysical properies. Membrane-less organelles in the nucleus of mammalian cells include the nucleolus, Cajal bodies and the so-called promyelocytic leukemia nuclear bodies (PML NBs). While the biochemical function of PML NBs is not yet elucidated these nuclear domains have been suggested to assemble and function via LLPS mechanisms, but in vivo evidence for this is lacking. With this research proposal we want to analyze the potential phase seperation features within PML bodies during homology-directed DNA recombination and repair of chromatin physically associated with the NBs. To this end we will combine biochemical and biophysical in vitro studies with advanced live-cell and super-resolution imaging technologies and computer modeling. These analyses shall prove our hypothesis that PML nuclear bodies serve as dedicated 'micro-reactors' where homologous DNA recombination is supported by concentrating specific DNA recombination and repair factors into active PML NBs by phase seperation.
DFG Programme
Priority Programmes
