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Updated: Mar 31, 2026

Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
The current state of eukaryotic DNA base damage and repair
Nicholas C Bauer1, Anita H Corbett2, Paul W Doetsch3
1Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA Graduate Program in Biochemistry, Cell, and Developmental Biology, Emory University School of Medicine, Atlanta, GA 30322, USA.
Abstract:
DNA damage is a natural hazard of life. The most common DNA lesions are base, sugar, and single-strand break damage resulting from oxidation, alkylation, deamination, and spontaneous hydrolysis. If left unrepaired, such lesions can become fixed in the genome as permanent mutations. Thus, evolution has led to the creation of several highly conserved, partially redundant pathways to repair or mitigate the effects of DNA base damage. The biochemical mechanisms of these pathways have been well characterized and the impact of this work was recently highlighted by the selection of Tomas Lindahl, Aziz Sancar and Paul Modrich as the recipients of the 2015 Nobel Prize in Chemistry for their seminal work in defining DNA repair pathways. However, how these repair pathways are regulated and interconnected is still being elucidated. This review focuses on the classical base excision repair and strand incision pathways in eukaryotes, considering both Saccharomyces cerevisiae and humans, and extends to some important questions and challenges facing the field of DNA base damage repair.
Insights
DNA damage is a constant threat, but cells possess repair pathways to prevent mutations. This review explores base excision repair and strand incision pathways in eukaryotes, highlighting current challenges in understanding their regulation.
Area of Science:
- Molecular Biology
- Genetics
- Biochemistry
Background:
- DNA damage is a natural occurrence from endogenous and exogenous sources.
- Common DNA lesions include base damage, sugar damage, and single-strand breaks.
- Unrepaired DNA damage can lead to mutations and genomic instability.
Purpose of the Study:
- To review classical base excision repair and strand incision pathways in eukaryotes.
- To discuss the regulation and interconnection of DNA repair pathways.
- To identify current challenges and future directions in DNA base damage repair research.
Main Methods:
- Literature review of established DNA repair mechanisms.
- Comparative analysis of DNA repair in Saccharomyces cerevisiae and humans.
- Discussion of regulatory networks and pathway crosstalk.
Main Results:
- Detailed characterization of base excision repair and strand incision pathways.
- Emphasis on the conserved nature and partial redundancy of DNA repair mechanisms.
- Identification of gaps in knowledge regarding the regulation and integration of these pathways.
Conclusions:
- DNA repair pathways are essential for maintaining genomic integrity.
- Further research is needed to fully elucidate the complex regulation and interplay of DNA repair pathways.
- Understanding these mechanisms is crucial for addressing diseases associated with DNA damage accumulation.
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