The post-translational modification poly(ADP-ribosyl)ation (PARylation) plays key roles in genome maintenance and transcription. Both non-covalent poly(ADP-ribose) binding and covalent PARylation control protein functions， however， it is unknown how the two modes of modification crosstalk mechanistically. Employing the tumor suppressor p53 as a model substrate， this study provides detailed insights into the interplay between non-covalent and covalent PARylation and unravels its functional significance in the regulation of p53. We reveal that the multifunctional C-terminal domain (CTD) of p53 acts as the central hub in the PARylation-dependent regulation of p53. Specifically， p53 bound to auto-PARylated PARP1 via highly specific non-covalent PAR-CTD interaction， which conveyed target specificity for its covalent PARylation by PARP1. Strikingly， fusing the p53-CTD to a protein that is normally not PARylated， renders this a target for covalent PARylation as well. Functional studies revealed that the p53-PAR interaction had substantial implications on molecular and cellular levels. Thus， PAR significantly influenced the complex p53-DNA binding properties and controlled p53 functions， with major implications on the p53-dependent interactome， transcription， and replication-associated recombination. Remarkably， this mechanism potentially also applies to other PARylation targets， since a bioinformatics analysis revealed that CTD-like regions are highly enriched in the PARylated proteome.