The study investigates the role of covalent poly-ADP-ribosylation (PARylation) of DNA base excision repair (BER) proteins by PARP1 and PARP2 in regulating DNA demethylation and repair. It is found that PARP1 senses AP-sites and single-strand breaks (SSBs) generated during TET-TDG-mediated active DNA demethylation and covalently attaches PAR to BER proteins, promoting their dissociation from DNA and accelerating the repair process. Inhibition of PARylation in mouse embryonic stem cells (mESC) results in reduced locus-specific TET-TDG-targeted DNA demethylation and general repair of random DNA damage. The study also demonstrates that PARylation reduces the affinity of BER proteins to DNA, facilitating their dissociation and turnover, which increases the overall efficiency of DNA demethylation. Additionally, PARylation of BER proteins interferes with their DNA binding, as shown by structural modeling. In U2OS cells, PARylation-deficient XRCC1 shows reduced recruitment to DNA damage sites compared to wild-type XRCC1. Overall, the findings highlight the critical role of covalent PARylation in coordinating molecular processes associated with dynamic DNA methylation and repair.The study investigates the role of covalent poly-ADP-ribosylation (PARylation) of DNA base excision repair (BER) proteins by PARP1 and PARP2 in regulating DNA demethylation and repair. It is found that PARP1 senses AP-sites and single-strand breaks (SSBs) generated during TET-TDG-mediated active DNA demethylation and covalently attaches PAR to BER proteins, promoting their dissociation from DNA and accelerating the repair process. Inhibition of PARylation in mouse embryonic stem cells (mESC) results in reduced locus-specific TET-TDG-targeted DNA demethylation and general repair of random DNA damage. The study also demonstrates that PARylation reduces the affinity of BER proteins to DNA, facilitating their dissociation and turnover, which increases the overall efficiency of DNA demethylation. Additionally, PARylation of BER proteins interferes with their DNA binding, as shown by structural modeling. In U2OS cells, PARylation-deficient XRCC1 shows reduced recruitment to DNA damage sites compared to wild-type XRCC1. Overall, the findings highlight the critical role of covalent PARylation in coordinating molecular processes associated with dynamic DNA methylation and repair.