THE ROLE OF DNA GLYCOSYLASES IN MAINTAINING GENOME STABILITY
https://doi.org/10.53360/2788-7995-2026-2(22)-49
Abstract
Genome stability is fundamental to cell viability, the evolutionary stability of organisms, and the preservation of their functional integrity. Endogenous damage, particularly the oxidative modification of nitrogenous bases resulting from cellular metabolism, is one of the main factors disrupting DNA structure. To prevent the accumulation of mutations, cells utilize a base excision repair (BER) system in which DNA glycosylases play a pivotal role. These enzymes recognize and remove damaged or mismatched bases, thereby initiating a cascade of repair reactions.
Adenine DNA glycosylases belonging to the MutY/MUTYH family are unique in that they do not directly remove damaged bases, but rather correct replication errors arising from oxidative damage to guanine. In bacteria, this function is performed by the MutY enzyme, whereas in eukaryotes it is performed by its homologue, MUTYH. These enzymes prevent G:C → T:A transition mutations from becoming fixed, thereby significantly reducing the level of spontaneous mutagenesis.
This review discusses the role of DNA glycosylases in maintaining genomic stability, focusing on the molecular mechanisms of adenine DNA glycosylase function, their place in the BER system, evolutionary conservation, and their significance in biotechnology, molecular genetics, and applied research.
About the Authors
U. SarsenbayevaKazakhstan
Ulan Sarsenbayeva – PhD student, Faculty of Biology and Biotechnology, 050040, Almaty, 71 Al-Farabi Avenue;
050012, Almaty, Dosmukhamedova 86;
050000, Almaty, Tole bi 94
A. Almasbekova
Kazakhstan
Adina Almasbekova – PhD student, Faculty of Biology and Biotechnology, 050040, Almaty, 71 Al-Farabi Avenue;
050012, Almaty, Dosmukhamedova 86;
050000, Almaty, Tole bi 94
K. Sharipov
Kazakhstan
Kamalidin Sharipov – Doctor of Biological Sciences, Professor and Director of the Institute, 050012, Almaty, Dosmukhamedova 86;
050000, Almaty, Tole bi 94
S. Taipakova
Kazakhstan
Sabira Taipakova – PhD, Associate Professor of the Department of Molecular Biology and Genetics,
050040, Almaty, 71 Al-Farabi Avenue
M. Saparbayev
Kazakhstan
Murat Saparbayev – candidate biological sciences, professor of the Department of Molecular Biology and Genetics,
050040, Almaty, 71 Al-Farabi Avenue
References
1. Jackson S.P. DNA-damage response signaling and cancer / S.P. Jackson, J. Bartek // Nature Reviews Molecular Cell Biology. – 2019. – Vol. 20, № 4. – P. 197-214. https://doi.org/10.1038/s41580-019-0135-3.
2. Hoeijmakers J.H.J. DNA damage, aging, and cancer / J.H.J. Hoeijmakers // New England Journal of Medicine. – 2016. – Vol. 377, № 7. – P. 640-649. https://doi.org/10.1056/NEJMra1604219.
3. Markkanen E. Not breathing is not an option: How to deal with oxidative DNA damage / E. Markkanen // DNA Repair. – 2017. – Vol. 59. – P. 82-105. https://doi.org/10.1016/j.dnarep.2017.09.002.
4. Sousa M.M.L. DNA glycosylases in genome maintenance and biotechnology / M.M.L. Sousa, H.E. Krokan, G. Slupphaug // Biotechnology Advances. – 2020. – Vol. 42. – 107579. https://doi.org/10.1016/j.biotechadv.2020.107579.
5. Krokan H.E. Base excision repair / H.E. Krokan, M. Bjørås // Cold Spring Harbor Perspectives in Biology. – 2013 (concept updated in recent reviews 2017–2021).
6. Krokan H.E. BER coordination and protein interactions / H.E. Krokan, A.B. Robertson // DNA Repair. – 2017. – Vol. 56. – P. 1-12. https://doi.org/10.1016/j.dnarep.2017.04.002.
7. DNA repair and transcriptional regulation / S. Amente et al // Trends in Genetics. – 2019. – Vol. 35, № 9. – P. 669-682. https://doi.org/10.1016/j.tig.2019.06.002.
8. Lirussi L. DNA Glycosylases Define the Outcome of Endogenous Base Modifications / L. Lirussi, H.L. Nilsen // International Journal of Molecular Sciences. – 2023. – Vol. 24, № 12. – Art. 10307. – https://doi.org/10.3390/ijms241210307.
9. Boiteux S. Repair of 8-oxoG lesions in DNA / S. Boiteux, F. Coste, B. Castaing // Free Radical Biology and Medicine. – 2017. – Vol. 107. – P. 1-12. https://doi.org/10.1016/j.freeradbiomed.2017.01.008.
10. Banda D.M. Repair of 8-oxoG:A mismatches by MUTYH / D.M. Banda, C.R.R. Rocha, C.F.M. Menck // Free Radical Biology and Medicine. – 2017. – Vol. 107. – P. 26-35. https://doi.org/10.1016/j.freeradbiomed.2017.01.008.
11. Oka S. MUTYH, cancer, and genome instability / S. Oka, J. Leon, D. Tsuchimoto // Mutation Research. – 2021. – Vol. 808. – 108423. https://doi.org/10.1016/j.mrrev.2021.108423.
12. van Loon B. An 8-oxoG perspective on mitochondrial genome instability / B. van Loon, U. Hübscher // DNA Repair. – 2019. – Vol. 75. – P. 52-60. https://doi.org/10.1016/j.dnarep.2019.02.006.
13. Mullins E.A. Toxicity and repair of oxidative DNA damage / E.A. Mullins, R. Shi, B.F. Eichman // Cellular and Molecular Life Sciences. – 2017. – Vol. 74, № 18. – P. 3367-3387. https://doi.org/10.1007/s00018-017-2478-8.
14. Oka S. DNA glycosylase encoded by MUTYH functions as a molecular switch for programmed cell death under oxidative stress to suppress tumorigenesis / S. Oka, Y. Nakabeppu // Cancer Science. – 2011. – Vol. 102, № 4. – P. 677-682. https://doi.org/10.1111/j.1349-7006.2011.01869.x.
15. Van Loon B. Аn 8-oxoG perspective on mitochondrial genome instability / B. van Loon, U. Hübscher // DNA Repair. – 2019. – Vol. 75. – P. 52-60. https://doi.org/10.1016/j.dnarep.2019.02.006.
16. Recent advances in the structural mechanisms of DNA glycosylases / S.C. Brooks et al // Biochimica et Biophysica Acta – Proteins and Proteomics. – 2013. – Vol. 1834. – P. 247-271.
17. Human POLβ gene mutation induces a mutator phenotype in mammalian cells / K.A. Donigan et al // Proceedings of the National Academy of Sciences USA. – 2016. – Vol. 113. – P. E2951-E2959. https://doi.org/10.1073/pnas.1520466113.
18. Focus on DNA Glycosylases – A Set of Tightly Regulated Enzymes with a High Potential as Anticancer Drug Targets / F. Hans et al // International Journal of Molecular Sciences. – 2020. – Vol. 21, № 23. – Art. 9226. https://doi.org/10.3390/ijms21239226.
19. Emerging Roles of DNA Glycosylases and the Base Excision Repair Pathway / E.A. Mullins et al // Trends in Biochemical Sciences. – 2019. – Vol. 44, № 9. – P. 765-781. https://doi.org/10.1016/j.tibs.2019.04.006.
20. Sobol R.W. Mammalian DNA base excision repair: Mechanisms and regulation / R.W. Sobol, S.H. Wilson // Progress in Molecular Biology and Translational Science. – 2020. – Vol. 168. – P. 1- 35. https://doi.org/10.1016/bs.pmbts.2019.12.003.
21. Dianov G.L. Mammalian base excision repair: The forgotten archangel / G.L. Dianov, U. Hübscher // Nucleic Acids Research. – 2013. – Vol. 41, № 6. – P. 3483-3490. https://doi.org/10.1093/nar/gkt076stress.
22. Sykora P. Base excision repair in the mammalian brain: Implication for age-related neurodegeneration / P. Sykora, D.M. Wilson, V.A. Bohr // Mechanisms of Ageing and Development. – 2018. – Vol. 174. – P. 19-27. https://doi.org/10.1016/j.mad.2017.11.001.
23. DNA glycosylases provide antiviral defence in prokaryotes / A.A. Hossain et al // Nature. – 2024. – Vol. 629. – P. 410-416.
24. Single molecule analysis indicates stimulation of MUTYH by UV-DDB through enzyme turnover / S. Jang et al // Nucleic Acids Research. – 2021. – Vol. 49, № 14. – P. 8177-8188. https://doi.org/10.1093/nar/gkab591.
25. 8-Oxoguanine: from oxidative damage to epigenetic and epitranscriptional modification / J.Y. Hahm et al // Experimental & Molecular Medicine. – 2022. – Vol. 54. – P. 1626-1642. https://doi.org/10.1038/s12276-022-00801-x.
26. Dynamics of 8-Oxoguanine in DNA: Decisive Effects of Base Pairing and Nucleotide Context / S.S. Ovcherenko et al // Journal of the American Chemical Society. – 2023. – Vol. 145, № 10. – P. 5201-5213. https://doi.org/10.1021/jacs.3c00421.
27. 8-Oxoguanine DNA Glycosylase1 conceals oxidized guanine in nucleoprotein-associated RNA of respiratory syncytial virus / L. Pan et al // PLoS Pathogens. – 2024. – Vol. 20, № 10. – Article e1012616. https://doi.org/10.1371/journal.ppat.1012616.
28. De Rosa M. Roles for the 8-Oxoguanine DNA Repair System in Protecting Telomeres From Oxidative Stress / M. De Rosa, S.A. Johnson, P.L. Opresko // Frontiers in Cell and Developmental Biology. – 2021. – Vol. 9. – Article 758402. https://doi.org/10.3389/fcell.2021.758402.
29. Cellular Repair of Synthetic Analogs of Oxidative DNA Damage Reveals a Key Structure–Activity Relationship of the Cancer Associated MUTYH DNA Repair Glycosylase / S.G. Conlon et al // ACS Central Science. – 2024. – Vol. 10, № 2. – P. 291-301. https://doi.org/10.1021/acscentsci.3c00784.
30. OGG1 and MUTYH repair activities promote telomeric 8-oxoguanine induced senescence in human fibroblasts / M. De Rosa et al // Nature Communications. – 2025. – Vol. 16. – Article 893. https://doi.org/10.1038/s41467-025-00345-2.
31. Structure of the mammalian adenine DNA glycosylase MUTYH: insights into the base excision repair pathway and cancer / T. Nakamura et al // Nucleic Acids Research. – 2021. – Vol. 49, № 12. – P. 7154-7163. https://doi.org/10.1093/nar/gkab492.
32. Energetic preference of 8-oxoG eversion pathways in a DNA glycosylase / C. Bergonzo et al // Journal of the American Chemical Society. – 2011. – Vol. 133, № 37. – P. 14504-14506. https://doi.org/10.1021/ja205142d.
33. Cellular repair of synthetic analogs of oxidative DNA damage reveals a key structure–activity relationship of the cancer-associated MUTYH DNA repair glycosylase / S.G. Conlon et al // ACS Central Science. – 2024. – Vol. 10, № 2. – P. 291-301. https://doi.org/10.1021/acscentsci.3c00784.
34. Embryonic lethal phenotype reveals a function of TDG in maintaining epigenetic stability / S. Cortellino et al // Nature. – 2011. – Vol. 470, № 7334. – P. 419-423. https://doi.org/10.1038/nature09672.
35. Dalton S.R. DNA demethylation by TDG / S.R. Dalton, A. Bellacosa // Epigenomics. – 2012. – Vol. 4, № 4. – P. 459-467. https://doi.org/10.2217/epi.12.36.
36. Helicobacter pylori infection downregulates the DNA glycosylase NEIL2, resulting in increased genome damage and inflammation in gastric epithelial cells / I.M. Sayed et al // Journal of Biological Chemistry. – 2020. – Vol. 295, № 32. – P. 11082-11098. https://doi.org/10.1074/jbc.RA120.013933.
37. Novel roles of DNA glycosylases in neurodegenerative diseases and aging / V. Tiwari et al // Neural Regeneration Research. – 2025. – Vol. 21, № 5. – P. 1991-1992. https://doi.org/10.4103/NRR.NRR-D-24-01588.
38. DNA repair glycosylase hNEIL1 triages damaged bases via competing interaction modes / Liu Menghao et al // Nature Communications. – 2021. – Vol. 12. – Article 4108. https://doi.org/10.1038/s41467-021-24431-y.
Review
For citations:
Sarsenbayeva U., Almasbekova A., Sharipov K., Taipakova S., Saparbayev M. THE ROLE OF DNA GLYCOSYLASES IN MAINTAINING GENOME STABILITY. Bulletin of Shakarim University. Technical Sciences. 2026;(2(22)):445-457. https://doi.org/10.53360/2788-7995-2026-2(22)-49
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