Accepted_test

HPF1 регулирует поли(ADP-рибозил)ирование РНК-связывающего белка FUS и влияет на образование поли(ADP-рибоза)-содержащих компартментов

by Anastasiya Singatulina | Maria Sukhanova | Olga Lavrik | Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences | Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences | Institute of Chemical Biology and Fundamental Medicine Siberian Branch of the Russian Academy of Sciences

Abstract ID: 372

Event: BGRS-abstracts

Sections: [Sym 11] Section “DNA replication and repair”

Currently, many RNA-binding proteins are considered to be involved in maintaining genome stability, since they are able to directly participate in DNA repair and can be attracted to the sites of DNA damage due to their interaction with poly(ADP-ribose). Poly(ADP-ribose) (PAR) is a negatively charged branched polymer consisting of ADP-ribose monomers. The synthesis of PAR from NAD⁺ is catalyzed by the enzymes poly(ADP-ribose) polymerases (PARPs), which are activated upon interaction with damaged DNA. The nuclear enzymes PARP1 and PARP2 catalyze auto-poly(ADP-ribosyl)ation (auto-PARylation), as well as PARylation of other target proteins.

Histone PARylation factor 1 (HPF1) was recently discovered as a co-factor of PARP1(2). HPF1 could form a temporary joint active site with PARP1(2), thereby changing the specificity of the PARylation reaction and regulating the level of PAR synthesis. Using atomic force microscopy (AFM), we have previously shown that RNA-binding protein FUS (FUS/TLS, Fused in Sarcoma) and PARylated PARP1 form supramolecular structures (compartments) in which damaged DNA is concentrated. In the current work we further investigated the effect of HPF1 on the activity of PARP1(2), PARylation of FUS and formation of compartments in the reconstituted system consisting of PARP1 or PARP2, HPF1 and FUS. FUS-dependent formation of compartments is of great interest for study, since FUS interacts with PAR and is able to localize at sites of DNA damage depending on PARP1 activation.