DNA Glycosylases in Noncancer Diseases: Oxidative Lesion Recognition, Repair Intermediates, and Tissue Responses
5 affiliations
- 1College of Pharmacy, Dongduk Women’s University, Seoul 02748, Republic of Korea
- 2College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea
- 3Graduate Program in Innovative Biomaterial Convergence, Ewha Womans University, Seoul 03760, Republic of Korea
- 4College of Pharmacy, Graduate School of Industrial Pharmaceutical Science, Ewha Womans University, Seoul 03760, Republic of Korea
- 5Graduate Program in Regulatory Science Convergence, Ewha Womans University, Seoul 03760, Republic of Korea
Abstract
Oxidative DNA damage in noncancer tissues can perturb transcription, compromise telomere integrity, and impair mitochondrial function. DNA glycosylases initiate base excision repair (BER), but their biological consequences also depend on lesion recognition, chromatin residence, catalytic processing, and the persistence or resolution of abasic sites and strand breaks. This review integrates structural and kinetic evidence with experimental models of inflammation, telomeric senescence, cardiometabolic disease, neurodegeneration, and neural injury. Promoter-associated 8-oxoguanine DNA glycosylase 1 (OGG1) can either promote inflammatory transcription or restrict antiviral interferon expression in a locus-dependent manner. At oxidatively damaged telomeres in human fibroblasts, OGG1 and mutY DNA glycosylase (MUTYH) drive acute senescence through repair intermediates, whereas during repeated injury, OGG1 supports telomere maintenance and MUTYH-dependent arrest limits chromosome instability. Mitochondria-directed OGG1 expression improves metabolic outcomes in OGG1-deficient mice exposed to a high-fat diet. By contrast, vascular and neural phenotypes associated with Nei-like DNA glycosylase 3 (NEIL3) remain difficult to attribute to a defined initiating lesion. These findings emphasize distinguishing enzyme occupancy, catalytic processing, and completed repair. Therapeutic studies should define the relevant cell, substrate, compartment, and exposure period and assess tissue function directly alongside unresolved lesions and chromosome stability.
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BibTeX
@article{kang2026glycosylases,
title = {{DNA Glycosylases in Noncancer Diseases: Oxidative Lesion Recognition, Repair Intermediates, and Tissue Responses}},
author = {Su-Jin Kang and Yubin Ko and Subin Cho and Sunbok Jang},
journal = {International Journal of Molecular Sciences},
year = {2026},
month = nov,
doi = {10.3390/ijms27219915},
url = {https://www.mdpi.com/1422-0067/27/21/9915},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - DNA Glycosylases in Noncancer Diseases: Oxidative Lesion Recognition, Repair Intermediates, and Tissue Responses
AU - Su-Jin Kang
AU - Yubin Ko
AU - Subin Cho
AU - Sunbok Jang
PY - 2026
DA - 2026/11/05
JO - International Journal of Molecular Sciences
DO - 10.3390/ijms27219915
UR - https://www.mdpi.com/1422-0067/27/21/9915
AB - Oxidative DNA damage in noncancer tissues can perturb transcription, compromise telomere integrity, and impair mitochondrial function. DNA glycosylases initiate base excision repair (BER), but their biological consequences also depend on lesion recognition, chromatin residence, catalytic processing, and the persistence or resolution of abasic sites and strand breaks. This review integrates structural and kinetic evidence with experimental models of inflammation, telomeric senescence, cardiometabolic disease, neurodegeneration, and neural injury. Promoter-associated 8-oxoguanine DNA glycosylase 1 (OGG1) can either promote inflammatory transcription or restrict antiviral interferon expression in a locus-dependent manner. At oxidatively damaged telomeres in human fibroblasts, OGG1 and mutY DNA glycosylase (MUTYH) drive acute senescence through repair intermediates, whereas during repeated injury, OGG1 supports telomere maintenance and MUTYH-dependent arrest limits chromosome instability. Mitochondria-directed OGG1 expression improves metabolic outcomes in OGG1-deficient mice exposed to a high-fat diet. By contrast, vascular and neural phenotypes associated with Nei-like DNA glycosylase 3 (NEIL3) remain difficult to attribute to a defined initiating lesion. These findings emphasize distinguishing enzyme occupancy, catalytic processing, and completed repair. Therapeutic studies should define the relevant cell, substrate, compartment, and exposure period and assess tissue function directly alongside unresolved lesions and chromosome stability.
SN - 1422-0067
ER -