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There has always been a lot of confusion about the intricate relationships between covalent and non-covalent poly(ADP-ribosylation) (PARylation).The exceptionally strong non-covalent interactions of PAR-binding proteins with ADP-ribose homopolymers have mostly been responsible for this confusion. The development of mass spectrometry (MS)-based detection of ADP-ribosylation events can now help us clarify the ADP-ribosylation status of PAR-associated proteins. Early proteomics studies were primarily identifying proteins with high affinity for PAR. We and others reported the identification of > 1000 PAR-associated proteins that were generally viewed as PAR-interacting proteins in a non-covalent fashion. Although this represents a large number of putative interactors, only …