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Updated: Nov 2, 2025
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
DNA damage and regulation of protein homeostasis
1The University of Texas at Austin, Department of Molecular Biosciences, Austin, TX, 78712, United States.
Abstract:
The accumulation of unrepaired DNA lesions is associated with many pathological outcomes in humans, particularly in neurodegenerative diseases and in normal aging. Evidence supporting a causal role for DNA damage in the onset and progression of neurodegenerative disease has come from rare human patients with mutations in DNA damage response genes as well as from model organisms; however, the generality of this relationship in the normal population is unclear. In addition, the relevance of DNA damage in the context of proteotoxic stress-the widely accepted paradigm for pathology during neurodegeneration-is not well understood. Here, observations supporting intertwined roles of DNA damage and proteotoxicity in aging-related neurological outcomes are reviewed, with particular emphasis on recent insights into the relationships between DNA repair and autophagy, the ubiquitin proteasome system, formation of protein aggregates, poly-ADP-ribose polymerization, and transcription-driven DNA lesions.
Insights
DNA damage accumulation contributes to neurodegeneration and aging. This review explores the links between DNA repair, proteotoxicity, and neurological decline, highlighting key cellular processes involved.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Accumulated DNA damage is linked to neurodegenerative diseases and aging.
- The role of DNA damage in the general population and its connection to proteotoxic stress in neurodegeneration requires further clarification.
Purpose of the Study:
- To review the intertwined roles of DNA damage and proteotoxicity in aging-related neurological outcomes.
- To emphasize recent findings on the relationships between DNA repair and key cellular pathways.
Main Methods:
- Literature review of studies on DNA damage, proteotoxicity, and neurodegeneration.
- Focus on mechanisms including DNA repair, autophagy, ubiquitin proteasome system, protein aggregation, and poly-ADP-ribose polymerization.
Main Results:
- DNA damage and proteotoxicity are interconnected in neurological aging.
- DNA repair pathways interact with proteostasis mechanisms like autophagy and the ubiquitin proteasome system.
- Transcription-driven DNA lesions and poly-ADP-ribose polymerization are implicated.
Conclusions:
- Understanding the interplay between DNA damage and proteotoxicity is crucial for addressing neurodegenerative diseases and aging.
- Targeting these interconnected pathways may offer therapeutic strategies for neurological disorders.
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