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Published on: September 5, 2017
Base excision repair of oxidative DNA damage: from mechanism to disease
Amy M Whitaker1, Matthew A Schaich1, Mallory R Smith1
1Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City, Kansas, 66160.
Abstract:
Reactive oxygen species continuously assault the structure of DNA resulting in oxidation and fragmentation of the nucleobases. Both oxidative DNA damage itself and its repair mediate the progression of many prevalent human maladies. The major pathway tasked with removal of oxidative DNA damage, and hence maintaining genomic integrity, is base excision repair (BER). The aphorism that structure often dictates function has proven true, as numerous recent structural biology studies have aided in clarifying the molecular mechanisms used by key BER enzymes during the repair of damaged DNA. This review focuses on the mechanistic details of the individual BER enzymes and the association of these enzymes during the development and progression of human diseases, including cancer and neurological diseases. Expanding on these structural and biochemical studies to further clarify still elusive BER mechanisms, and focusing our efforts toward gaining an improved appreciation of how these enzymes form co-complexes to facilitate DNA repair is a crucial next step toward understanding how BER contributes to human maladies and how it can be manipulated to alter patient outcomes.
Insights
Base excision repair (BER) removes oxidative DNA damage, crucial for preventing diseases like cancer. Recent structural studies clarify BER enzyme mechanisms, aiding disease understanding and therapeutic strategies.
Area of Science:
- Molecular Biology
- Genomics
- Biochemistry
Background:
- Reactive oxygen species cause DNA damage, contributing to human diseases.
- Base excision repair (BER) is the primary pathway for removing oxidative DNA damage.
- Genomic integrity is maintained by efficient DNA repair mechanisms.
Purpose of the Study:
- To review the mechanistic details of individual base excision repair (BER) enzymes.
- To explore the role of BER enzymes in the development and progression of human diseases, including cancer and neurological disorders.
- To highlight the importance of structural and biochemical studies in understanding BER.
Main Methods:
- Review of recent structural biology studies on BER enzymes.
- Analysis of biochemical data elucidating BER enzyme mechanisms.
- Integration of findings to connect BER to human disease pathology.
Main Results:
- Recent structural studies have clarified the molecular mechanisms of key BER enzymes.
- Understanding BER enzyme function is critical for comprehending disease progression.
- BER enzyme associations and co-complex formation are vital for efficient DNA repair.
Conclusions:
- Elucidating the precise mechanisms of BER enzymes and their co-complexes is essential for understanding their role in human maladies.
- Further research into BER pathways can lead to novel therapeutic strategies for cancer and neurological diseases.
- Manipulating BER activity holds potential for altering patient outcomes in various diseases.
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