Enzymatic Processing of DNA–Protein Crosslinks

Maram M. Essawy, Colin Campbell

Research output: Contribution to journalReview articlepeer-review

Abstract

DNA–protein crosslinks (DPCs) represent a unique and complex form of DNA damage formed by covalent attachment of proteins to DNA. DPCs are formed through a variety of mechanisms and can significantly impede essential cellular processes such as transcription and replication. For this reason, anti-cancer drugs that form DPCs have proven effective in cancer therapy. While cells rely on numerous different processes to remove DPCs, the molecular mechanisms responsible for orchestrating these processes remain obscure. Having this insight could potentially be harnessed therapeutically to improve clinical outcomes in the battle against cancer. In this review, we describe the ways cells enzymatically process DPCs. These processing events include direct reversal of the DPC via hydrolysis, nuclease digestion of the DNA backbone to delete the DPC and surrounding DNA, proteolytic processing of the crosslinked protein, as well as covalent modification of the DNA-crosslinked proteins with ubiquitin, SUMO, and Poly(ADP) Ribose (PAR).

Original languageEnglish (US)
Article number85
JournalGenes
Volume15
Issue number1
DOIs
StatePublished - Jan 2024

Bibliographical note

Publisher Copyright:
© 2024 by the authors.

Keywords

  • DNA–protein crosslink (DPC)
  • SPRTN
  • SUMO
  • direct crosslink reversal
  • nuclease
  • poly(ADP) ribose (PAR)
  • protease
  • proteasome
  • ubiquitin

PubMed: MeSH publication types

  • Journal Article
  • Review

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