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. Author manuscript; available in PMC: 2023 Jun 16.
Published in final edited form as: Mol Cell. 2022 Mar 9;82(12):2315–2334. doi: 10.1016/j.molcel.2022.02.021

Figure 5. Emerging concepts and mechanisms of PARP1-dependent regulation.

Figure 5.

(A) PAR-dependent PTMs. PAR-dependent protein-protein interactions can drive substrates to their cognate modifying enzymes. Examples include (1) “PAR-dependent PARylation,” where a substrate protein interacts with automodified PARP1 through PAR, leading to subsequent PARylation of the substrate protein by PARP1 and (2) other “PAR-dependent post-translational modifications,” where a PARP (e.g., PARP1, PARP5) interacts with and PARylates a substrate protein, which promotes PAR-dependent interactions with a modifying enzyme, leading to posttranslational modification (e.g., ubiquitylation, phosphorylation) of the PARP substrate protein by that modifying enzyme.

(B) ADPR spray. ADPRylation events mediated by nuclear PARP1 may drive a high density “ADPR spray” across key histone and accessory proteins in processes including DNA repair, chromatin modulation, and transcription.

(C) PAR-mediated biomolecular condensate formation and function. Free or protein-linked PAR may regulate the formation or dissociation of biomolecular condensates. In this example, PAR facilitates the phase separation of FUS, TDP43, and hnRNPA1 to form stress granules (SG) in the pathogenesis of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD).