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Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
10:12

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications

Published on: April 21, 2023

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Targeting DNA-Protein Crosslinks via Post-Translational Modifications

Xueyuan Leng1, Julien P Duxin1

  • 1The Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

Frontiers in Molecular Biosciences
|July 21, 2022
PubMed

Insights

DNA-protein crosslinks (DPCs) are cytotoxic lesions repaired through various pathways. Post-translational modifications (PTMs) like ubiquitylation, SUMOylation, and PARylation are crucial for orchestrating DPC removal, even without DNA replication.

Area of Science:

  • Molecular Biology
  • Genetics
  • Biochemistry

Background:

  • DNA-protein crosslinks (DPCs) are cytotoxic DNA lesions that impede DNA replication and transcription.
  • Cellular mechanisms exist to counteract DPCs, involving protein degradation, crosslink resolution, or DNA incision.
  • Understanding DPC sensing and targeted removal pathways is critical.

Purpose of the Study:

  • To review current knowledge on mechanisms triggering DPC removal via post-translational modifications (PTMs).
  • To focus on ubiquitylation, SUMOylation, and PARylation in DPC repair.
  • To identify knowledge gaps and emerging hypotheses in DPC repair.

Main Methods:

  • Literature review of DPC repair mechanisms.
  • Focus on the role of PTMs in DPC removal.
  • Analysis of ubiquitylation, SUMOylation, and PARylation pathways.

Main Results:

  • DPC removal can be triggered by DNA replication via proteolysis.
  • DPCs are also efficiently removed in the absence of DNA replication.
  • PTMs, including ubiquitylation, SUMOylation, and PARylation, are essential for orchestrating DPC repair routes.

Conclusions:

  • PTMs play versatile and essential roles in directing DPC removal pathways.
  • Further research is needed to address current knowledge gaps and explore emerging hypotheses in DPC repair.
  • The interplay between DNA replication and PTMs in DPC processing requires further elucidation.
Keywords:
DNA repairDNA replicationDNA-protein crosslink (DPC)poly(ADP-ribosyl)ationpost-translational modifications (PTMs)small ubiquitin-related modifier (SUMO)ubiquitylation

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