DNA Repair Mechanisms Involving Glycosylase Activity

The maintenance of genomic integrity relies critically on the base excision repair (BER) pathway, which rectifies small-scale lesions arising from oxidation, alkylation or deamination. Central to BER are DNA glycosylases, specialised enzymes that scan the double helix, recognise altered bases, and cleave the N-glycosidic bond to generate an abasic or apurinic/apyrimidinic (AP) site. Following glycosylase action, AP endonucleases incise the sugar-phosphate backbone, allowing DNA polymerases to fill the gap and ligases to restore strand continuity. Glycosylases display remarkable substrate specificity through a combination of lesion detection via base flipping and active-site discrimination of chemical moieties such as the 2-amino group of 8-oxoguanine. Variants or dysregulation of glycosylases can lead to mutagenic persistence of mispairs, prompting transversion mutations and contributing to cancer predisposition syndromes and age-related disease. Advances in structural biology and single-molecule analyses have elucidated how conserved loops and recognition domains enable rapid lesion scanning while avoiding non-target bases. Understanding glycosylase mechanics not only informs the etiology of hereditary disorders but also underpins emerging diagnostic tools, small-molecule inhibitors and therapeutic strategies aimed at modulating repair activity in cancer and degenerative conditions.

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DNA Repair Mechanisms Involving Glycosylase Activity publication trend

The graph below shows the total number of articles in dna repair mechanisms involving glycosylase activity across all publications each year (not limited to Nature Index journals).

Technical terms

Base excision repair (BER): Pathway that removes and replaces damaged bases in DNA to maintain genomic stability.

DNA glycosylase: Enzyme that recognises and excises modified bases, initiating BER by creating an AP site.

8-oxoguanine (8-oxoG): Common oxidative lesion formed on guanine that can mispair with adenine.

Apurinic/apyrimidinic (AP) site: Abasic location in DNA resulting from removal of a damaged base, requiring further processing.

Mismatch: Incorrect pairing between nucleotides that can lead to mutations if unrepaired.

References

1. FSHing for DNA Damage: Key Features of MutY Detection of 8‑Oxoguanine:Adenine Mismatches. Accounts of Chemical Research (2024).
2. HUWE1‐Mediated Degradation of MUTYH Facilitates DNA Damage and Mitochondrial Dysfunction to Promote Acute Kidney Injury. Advanced Science (2025).
3. Cellular Repair of Synthetic Analogs of Oxidative DNA Damage Reveals a Key Structure–Activity Relationship of the Cancer-Associated MUTYH DNA Repair Glycosylase. ACS Central Science (2024).