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Updated: Sep 8, 2025

Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
A field guide to the proteomics of post-translational modifications in DNA repair
Ethan James Sanford1, Marcus Bustamante Smolka1
1Department of Molecular Biology and Genetics, Weill Institute for Cell and Molecular Biology, Cornell University, Ithaca, New York, USA.
Abstract:
All cells incur DNA damage from exogenous and endogenous sources and possess pathways to detect and repair DNA damage. Post-translational modifications (PTMs), in the past 20 years, have risen to ineluctable importance in the study of the regulation of DNA repair mechanisms. For example, DNA damage response kinases are critical in both the initial sensing of DNA damage as well as in orchestrating downstream activities of DNA repair factors. Mass spectrometry-based proteomics revolutionized the study of the role of PTMs in the DNA damage response and has canonized PTMs as central modulators of nearly all aspects of DNA damage signaling and repair. This review provides a biologist-friendly guide for the mass spectrometry analysis of PTMs in the context of DNA repair and DNA damage responses. We reflect on the current state of proteomics for exploring new mechanisms of PTM-based regulation and outline a roadmap for designing PTM mapping experiments that focus on the DNA repair and DNA damage responses.
Insights
Cells use post-translational modifications (PTMs) to regulate DNA repair. This review guides biologists on using mass spectrometry proteomics to study PTMs in DNA damage responses.
Area of Science:
- Molecular Biology
- Biochemistry
- Proteomics
Background:
- Cells constantly face DNA damage from various sources.
- Post-translational modifications (PTMs) are crucial regulators of DNA repair pathways.
- DNA damage response kinases play key roles in sensing damage and coordinating repair.
Purpose of the Study:
- To provide a biologist-friendly guide to mass spectrometry analysis of PTMs in DNA repair.
- To review the current state of proteomics in understanding PTM-based regulation of DNA damage response.
- To outline a roadmap for designing PTM mapping experiments in DNA repair research.
Main Methods:
- Mass spectrometry-based proteomics is highlighted as a revolutionary technique.
- Discussion of experimental design for PTM mapping in DNA damage contexts.
- Focus on analyzing PTMs involved in DNA damage signaling and repair.
Main Results:
- Proteomics has established PTMs as central modulators of DNA damage signaling and repair.
- Mass spectrometry enables detailed study of PTMs' roles in DNA repair mechanisms.
- Current proteomics approaches allow exploration of novel PTM-based regulatory mechanisms.
Conclusions:
- PTMs are indispensable for regulating DNA repair mechanisms.
- Mass spectrometry proteomics is a powerful tool for investigating PTMs in DNA damage response.
- Future research should focus on designing targeted PTM mapping experiments to uncover new regulatory insights.
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