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Updated: Feb 28, 2026

Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy
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Characterizing DNA Repair Processes at Transient and Long-lasting Double-strand DNA Breaks by Immunofluorescence Microscopy

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Cellular strategies for repairing trapped protein-DNA complexes

Maria Sideridou1,2, Doukissa Ioanna Machli1, Dora Lontra1

  • 1Biomedical Research Foundation, Academy of Athens, Athens, Greece.

Frontiers in Pharmacology
|February 26, 2026
PubMed

Insights

DNA-protein crosslinks (DPCs) are toxic lesions repaired by specialized cellular mechanisms. Understanding DPC repair is crucial for developing effective cancer therapies and overcoming drug resistance.

Area of Science:

  • Molecular Biology
  • Cancer Biology
  • Biochemistry

Background:

  • DNA-protein crosslinks (DPCs) are toxic DNA lesions formed during normal metabolism and cancer chemotherapy.
  • Anticancer drugs like topoisomerase poisons and PARP inhibitors induce DPCs by trapping enzymes on DNA, creating replication barriers.

Purpose of the Study:

  • To review the molecular mechanisms of DPC formation by anticancer therapies.
  • To explore cellular defense systems for DPC detection and resolution.
  • To examine the role of DPC repair in cancer and its implications for treatment.

Main Methods:

  • Literature review of molecular mechanisms.
  • Analysis of cellular DPC repair pathways.
  • Integration of mechanistic insights with clinical data on cancer treatment.

Main Results:

  • Cells employ multi-layered defense systems, including enzymatic degradation and mechanical extraction, to resolve DPCs.
  • DPC repair processes are modulated by the cell cycle and chromatin structure.
  • Alterations in DPC repair pathways are common in cancer and influence treatment response.

Conclusions:

  • Exploiting DPC repair defects offers a strategy to overcome drug resistance in cancer.
  • Understanding DPC repair is key to developing rational, synthetic lethal combination therapies.
Keywords:
DNA repairPARP inhibitorscancerchemotherapyprotein-DNA crosslinkstopoisomerase poisons

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