Figure 4.

Model connecting ARP2/3-dependent movements and PAR-dependent liquid–liquid phase separation. Several classes of proteins are dynamically parylated at sites of DNA damage (top) through the balanced actions of poly(ADP-ribose) polymerases (PARPs) and poly(ADP-ribose) glycohydrolase (PARG). Red circles indicate proteins interacting with PAR, such as BRCT-containing proteins (BRCA1/2), parylated proteins (hnRNPs/FUS), or IDPs that associate via PAR. We propose that “random” movements generated by Arp2/3-dependent actin polymerization facilitate interactions among parylated proteins, PAR-interacting proteins, and IDPs, which together facilitate liquid–liquid phase separation of DSB repair domains surrounding multiple DSBs.

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