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Updated: Nov 23, 2025
Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
DNA-protein crosslink proteases in genome stability
Annamaria Ruggiano1, Kristijan Ramadan2
1Medical Research Council (MRC) Oxford Institute for Radiation Oncology, Department of Oncology, University of Oxford, Roosevelt Drive, OX3 7DQ, Oxford, UK.
Abstract:
Proteins covalently attached to DNA, also known as DNA-protein crosslinks (DPCs), are common and bulky DNA lesions that interfere with DNA replication, repair, transcription and recombination. Research in the past several years indicates that cells possess dedicated enzymes, known as DPC proteases, which digest the protein component of a DPC. Interestingly, DPC proteases also play a role in proteolysis beside DPC repair, such as in degrading excess histones during DNA replication or controlling DNA replication checkpoints. Here, we discuss the importance of DPC proteases in DNA replication, genome stability and their direct link to human diseases and cancer therapy.
Insights
DNA-protein crosslinks (DPCs) are harmful DNA lesions. Dedicated DPC proteases repair these lesions and regulate DNA replication and genome stability, impacting cancer therapy.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA-protein crosslinks (DPCs) are bulky DNA lesions impeding essential DNA processes like replication and transcription.
- Cells have evolved specialized enzymes, DPC proteases, to resolve these complex DNA lesions.
Purpose of the Study:
- To review the critical roles of DPC proteases in DNA replication and genome stability.
- To highlight the connection between DPC proteases, human diseases, and cancer treatment strategies.
Main Methods:
- Literature review of recent research on DPC proteases.
- Analysis of the functions of DPC proteases beyond DPC repair.
Main Results:
- DPC proteases are essential for resolving DPCs, facilitating DNA replication, repair, transcription, and recombination.
- These enzymes also regulate histone degradation during DNA replication and control DNA replication checkpoints.
- Dysfunctional DPC proteases are linked to human diseases and cancer development.
Conclusions:
- DPC proteases are crucial for maintaining genome integrity and cellular function.
- Targeting DPC proteases presents a promising avenue for novel cancer therapies.
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