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DNA Repair and Disease: Insights from the Human DNA Glycosylase NEIL Family

Overview
Journal Exp Mol Med
Date 2025 Mar 3
PMID 40033009
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Abstract

The base excision repair pathway protects DNA from base damage via oxidation, deamination, alkylation and methylation. DNA glycosylases are key enzymes that recognize damaged bases in a lesion-specific manner and initiate the base excision repair process. Among these, the endonuclease VIII-like 1-3 (NEIL1-3) family, which is found in mammalian genomes, is a homolog of bacterial DNA glycosylases known as Fpg/Nei. NEIL enzymes have similar structures and substrates but with slight differences. When repair proteins are impaired, the accumulation of damaged bases can lead to increased genomic instability, which is implicated in various pathologies, including cancer and neurodegeneration. Notably, mutations in these proteins also influence a range of other diseases and inflammation. This review focuses on the influence of the NEIL family on human health across different organ systems. Investigating the relationship between NEIL mutations and diseases can improve our understanding of how these enzymes affect the human body. This information is crucial for understanding the basic mechanisms of DNA repair and enabling the development of novel inhibitors or gene therapies that target only these enzymes. Understanding the role of the NEIL family provides insights into novel therapies and improves our ability to combat genetic diseases.

References
1.
Kim Y, Wilson 3rd D . Overview of base excision repair biochemistry. Curr Mol Pharmacol. 2011; 5(1):3-13. PMC: 3459583. DOI: 10.2174/1874467211205010003. View

2.
Wallace S, Murphy D, Sweasy J . Base excision repair and cancer. Cancer Lett. 2012; 327(1-2):73-89. PMC: 3361536. DOI: 10.1016/j.canlet.2011.12.038. View

3.
Lindahl T, Wood R . Quality control by DNA repair. Science. 1999; 286(5446):1897-905. DOI: 10.1126/science.286.5446.1897. View

4.
Krokan H, Standal R, Slupphaug G . DNA glycosylases in the base excision repair of DNA. Biochem J. 1997; 325 ( Pt 1):1-16. PMC: 1218522. DOI: 10.1042/bj3250001. View

5.
Mitra S . DNA glycosylases: specificity and mechanisms. Prog Nucleic Acid Res Mol Biol. 2001; 68:189-92. DOI: 10.1016/s0079-6603(01)68099-1. View