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Updated: Feb 19, 2026
A Simple, Rapid, and Quantitative Assay to Measure Repair of DNA-protein Crosslinks on Plasmids Transfected into Mammalian Cells
Published on: March 5, 2018
Formation and repair of DNA-protein crosslink damage
Naeh L Klages-Mundt1,2, Lei Li3,4
1Department of Experimental Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, 77030, USA.
Abstract:
DNA is constantly exposed to a wide array of genotoxic agents, generating a variety of forms of DNA damage. DNA-protein crosslinks (DPCs)-the covalent linkage of proteins with a DNA strand-are one of the most deleterious and understudied forms of DNA damage, posing as steric blockades to transcription and replication. If not properly repaired, these lesions can lead to mutations, genomic instability, and cell death. DPCs can be induced endogenously or through environmental carcinogens and chemotherapeutic agents. Endogenously, DPCs are commonly derived through reactions with aldehydes, as well as through trapping of various enzymatic intermediates onto the DNA. Proteolytic cleavage of the protein moiety of a DPC is a general strategy for removing the lesion. This can be accomplished through a DPC-specific protease and and/or proteasome-mediated degradation. Nucleotide excision repair and homologous recombination are each involved in repairing DPCs, with their respective roles likely dependent on the nature and size of the adduct. The Fanconi anemia pathway may also have a role in processing DPC repair intermediates. In this review, we discuss how these lesions are formed, strategies and mechanisms for their removal, and diseases associated with defective DPC repair.
Insights
DNA-protein crosslinks (DPCs) are harmful DNA lesions blocking replication and transcription. This review covers DPC formation, repair mechanisms like proteolysis and DNA repair pathways, and associated diseases.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA is susceptible to damage from genotoxic agents.
- DNA-protein crosslinks (DPCs) are a particularly deleterious and understudied form of DNA damage.
- DPCs impede essential cellular processes like transcription and replication, potentially leading to mutations, genomic instability, and cell death.
Purpose of the Study:
- To review the formation, repair, and disease implications of DNA-protein crosslinks (DPCs).
- To elucidate the mechanisms underlying DPC generation and removal.
- To highlight the roles of various DNA repair pathways in processing DPCs.
Main Methods:
- Literature review of DNA-protein crosslink (DPC) research.
- Analysis of DPC formation pathways, including endogenous and exogenous sources.
- Examination of DPC repair mechanisms, involving proteolysis, nucleotide excision repair, homologous recombination, and the Fanconi anemia pathway.
Main Results:
- DPCs can be induced by aldehydes and trapped enzymatic intermediates.
- Proteolytic cleavage, including DPC-specific proteases and proteasome-mediated degradation, is a key removal strategy.
- Nucleotide excision repair, homologous recombination, and the Fanconi anemia pathway are implicated in DPC repair, with roles dependent on adduct characteristics.
Conclusions:
- Understanding DPC formation and repair is crucial for addressing genomic instability and associated diseases.
- Defective DPC repair is linked to various pathological conditions.
- Further research into DPC repair mechanisms is warranted to develop therapeutic strategies.
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