The Complex Network of ADP-Ribosylation and DNA Repair: Emerging Insights and Implications for Cancer Therapy

Int J Mol Sci. 2023 Oct 9;24(19):15028. doi: 10.3390/ijms241915028.

Abstract

ADP-ribosylation is a post-translational modification of proteins that plays a key role in various cellular processes, including DNA repair. Recently, significant progress has been made in understanding the mechanism and function of ADP-ribosylation in DNA repair. ADP-ribosylation can regulate the recruitment and activity of DNA repair proteins by facilitating protein-protein interactions and regulating protein conformations. Moreover, ADP-ribosylation can influence additional post-translational modifications (PTMs) of proteins involved in DNA repair, such as ubiquitination, methylation, acetylation, phosphorylation, and SUMOylation. The interaction between ADP-ribosylation and these additional PTMs can fine-tune the activity of DNA repair proteins and ensure the proper execution of the DNA repair process. In addition, PARP inhibitors have been developed as a promising cancer therapeutic strategy by exploiting the dependence of certain cancer types on the PARP-mediated DNA repair pathway. In this paper, we review the progress of ADP-ribosylation in DNA repair, discuss the crosstalk of ADP-ribosylation with additional PTMs in DNA repair, and summarize the progress of PARP inhibitors in cancer therapy.

Keywords: ADP-ribosylation; DNA damage and repair; PARP inhibitors; cancer therapy; post-translational modification.

Publication types

  • Review

MeSH terms

  • ADP-Ribosylation
  • DNA Repair
  • Humans
  • Neoplasms* / drug therapy
  • Neoplasms* / genetics
  • Poly(ADP-ribose) Polymerase Inhibitors / pharmacology
  • Poly(ADP-ribose) Polymerase Inhibitors / therapeutic use
  • Poly(ADP-ribose) Polymerases* / metabolism
  • Protein Processing, Post-Translational
  • Proteins / metabolism

Substances

  • Poly(ADP-ribose) Polymerases
  • Poly(ADP-ribose) Polymerase Inhibitors
  • Proteins