Immunoprecipitated PARP1 interactome

Poly-(ADP-ribose) polymerase inhibitors (PARPi) elicit anti-tumour activity in homologous recombination defective cancers by promoting cytotoxic, chromatin-bound, “trapped” PARP1 DNA lesions. How cells process trapped PARP1 remains unclear. By exploiting wild-type or trapping-resistant PARP1 transgenes combined with rapid immunoprecipitation mass-spectrometry of endogenous proteins (RIME) and Apex2-proximity labelling, we generated proteomic profiles of trapped and non-trapped PARP1 complexes. This combined approach identified an interaction between PARP1 and the ubiquitin system including its central component - the ubiquitin-regulated p97 ATPase (aka VCP).