Dresden 2020 – scientific programme

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BP: Fachverband Biologische Physik

BP 2: Focus: Phase Separation in Biological Systems I (joint session BP/CPP)

BP 2.1: Talk

Monday, March 16, 2020, 09:30–09:45, SCH A251

ATP-arrested phase separation of an abundant nuclear protein — •Davide Michieletto — University of Bath

The formation and regulation of phase separated condensates is an important and ubiquitous process in biology. However, the biological functions of these condensates and how they are regulated, i.e. assembled and disassembled in vivo, are still poorly understood

I will present our recent work on an abundant nuclear protein called Scaffold Attachment Factor A, or SAF-A, that is involved in organizing the genome. It contains an intrinsically disordered RNA binding domain and an ATP-binding and hydrolysis domain. We discovered that the RGG domain of this protein undergoes phase separation in the nucleus upon transcriptional inhibition and that the size of the droplets can be controlled by tuning the amount arginine/lysine residues in the RGG domain and, more importantly, the coarsening of these droplets is arrested when the RGG domain is fused with the ATPase domain. To explain our findings, we propose a non-equilibrium extension of the classical Model B equations in which AAA-RGG fragments can switch between binding and non-binding states.

In summary, we provide evidence that not only does SAF-A undergo phase separation but we are able to show that this behavior can be regulated using an ATP-switch linked to its functional role in the nucleus.