Related Experiment Video
Updated: Sep 29, 2025
Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
DNA-Protein Crosslinks and Their Resolution
Pedro Weickert1,2, Julian Stingele1,2
1Department of Biochemistry, Ludwig Maximilians University, Munich, Germany;
Abstract:
Covalent DNA-protein crosslinks (DPCs) are pervasive DNA lesions that interfere with essential chromatin processes such as transcription or replication. This review strives to provide an overview of the sources and principles of cellular DPC formation. DPCs are caused by endogenous reactive metabolites and various chemotherapeutic agents. However, in certain conditions DPCs also arise physiologically in cells. We discuss the cellular mechanisms resolving these threats to genomic integrity. Detection and repair of DPCs require not only the action of canonical DNA repair pathways but also the activity of specialized proteolytic enzymes-including proteases of the SPRTN/Wss1 family-to degrade the crosslinked protein. Loss of DPC repair capacity has dramatic consequences, ranging from genome instability in yeast and worms to cancer predisposition and premature aging in mice and humans.
Insights
DNA-protein crosslinks (DPCs) are harmful DNA lesions. Specialized repair mechanisms, including proteases, are crucial for resolving DPCs and maintaining genomic integrity, preventing diseases like cancer.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- Covalent DNA-protein crosslinks (DPCs) are significant DNA lesions impacting vital cellular processes like transcription and replication.
- DPCs can originate from endogenous metabolites, chemotherapeutic drugs, or physiological conditions.
Purpose of the Study:
- To review the sources and formation principles of cellular DPCs.
- To outline the cellular mechanisms involved in DPC resolution and repair.
Main Methods:
- Literature review of DPC formation, detection, and repair pathways.
- Discussion of the role of canonical DNA repair and specialized proteases (e.g., SPRTN/Wss1 family).
Main Results:
- DPCs arise from various endogenous and exogenous sources, including physiological states.
- Repair necessitates both DNA repair pathways and proteolytic degradation of crosslinked proteins.
- Loss of DPC repair capacity leads to genome instability and disease.
Conclusions:
- Effective DPC resolution is critical for maintaining genomic integrity.
- Dysfunctional DPC repair is linked to severe health consequences, including cancer predisposition and premature aging.
- Proteolytic enzymes play a key role in mitigating DPC-induced cellular damage.
More Related Videos
12:43Advanced Confocal Microscopy Techniques to Study Protein-protein Interactions and Kinetics at DNA Lesions
Published on: November 12, 2017
10:01Combining Chemical Cross-linking and Mass Spectrometry of Intact Protein Complexes to Study the Architecture of Multi-subunit Protein Assemblies
Published on: November 28, 2017