Figure 4.

Inhibition of RNF4. (A) Functioning RNF4. The E3 ligase RNF4 recognizes small ubiquitin-like modifier (SUMO)-ylated mediator of DNA damage checkpoint protein 1 (MDC1) and replication protein A (RPA), labelling them for proteasomal degradation, resulting in; activation of Ataxia telangiectasia mutated kinase (ATM) and loading of Rad51 onto DNA. RNF4 mediated ubiquitination allows for successful HR repair. (B) Inhibition of RNF4 results in a homologous recombination (HR) defect, leading to an increased sensitivity to PARP inhibitors.