Unknown

Dataset Information

0

PARylation prevents the proteasomal degradation of topoisomerase I DNA-protein crosslinks and induces their deubiquitylation.


ABSTRACT: Poly(ADP)-ribosylation (PARylation) regulates chromatin structure and recruits DNA repair proteins. Using single-molecule fluorescence microscopy to track topoisomerase I (TOP1) in live cells, we found that sustained PARylation blocked the repair of TOP1 DNA-protein crosslinks (TOP1-DPCs) in a similar fashion as inhibition of the ubiquitin-proteasome system (UPS). PARylation of TOP1-DPC was readily revealed by inhibiting poly(ADP-ribose) glycohydrolase (PARG), indicating the otherwise transient and reversible PARylation of the DPCs. As the UPS is a key repair mechanism for TOP1-DPCs, we investigated the impact of TOP1-DPC PARylation on the proteasome and found that the proteasome is unable to associate with and digest PARylated TOP1-DPCs. In addition, PARylation recruits the deubiquitylating enzyme USP7 to reverse the ubiquitylation of PARylated TOP1-DPCs. Our work identifies PARG as repair factor for TOP1-DPCs by enabling the proteasomal digestion of TOP1-DPCs. It also suggests the potential regulatory role of PARylation for the repair of a broad range of DPCs.

SUBMITTER: Sun Y 

PROVIDER: S-EPMC8373905 | biostudies-literature |

REPOSITORIES: biostudies-literature

Similar Datasets

| S-EPMC4857006 | biostudies-literature
| S-EPMC7673754 | biostudies-literature
| S-EPMC7293035 | biostudies-literature
| S-EPMC3939901 | biostudies-literature
| S-EPMC9975044 | biostudies-literature
| S-EPMC8754632 | biostudies-literature
2023-11-13 | GSE240136 | GEO
| S-EPMC7511601 | biostudies-literature
| S-EPMC2546926 | biostudies-literature
| S-EPMC6697639 | biostudies-literature