| Gene |
NEIL2 |
| UniProt |
Q96S44 |
| Molecular Weight |
40 kDa |
| Subcellular Localization |
Nucleus, Mitochondria |
| Protein Family |
FPG/Nei DNA Glycosylase Family |
Neil2 Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
NEIL2 (Nei Endonuclease VIII-Like 2) is a DNA glycosylase that initiates the base excision repair (BER) pathway by recognizing and removing damaged bases from DNA. Unlike other DNA glycosylases, NEIL2 has a unique substrate specificity and is particularly important for repairing oxidative DNA damage in transcribed regions and mitochondrial DNA.
NEIL2 contains characteristic domains:
- Fpg/Nei Domain: Catalytic core with the helix-hairpin-helix (HhH) motif
- Iron-Sulfur Cluster Binding Site: [4Fe-4S] cluster for structural stability
- Proline Insertion: Unique proline-rich insertion that may contribute to substrate specificity
- C-terminal Tail: Involved in protein-protein interactions
The active site contains a zinc finger motif important for DNA binding.
NEIL2 removes a broad range of oxidized base lesions:
- 5-hydroxyuracil (5-OHU)
- 8-oxoguanine (8-oxoG)
- Fapy-guanine (FapyG)
- 5-hydroxycytosine (5-OHC)
- Thymine glycol (Tg)
- Associates with RNA polymerase II during transcription
- Prioritizes repair of DNA lesions in actively transcribed genes
- Couples transcription to DNA repair (TCR)
- Translocates to mitochondria
- Maintains mitochondrial genome integrity
- Protects against mtDNA mutations
- Critical for repair of oxidative DNA damage in neurons
- Required for synaptic plasticity and cognitive function
- Protects against age-related cognitive decline
NEIL2 deficiency contributes to:
- Accumulation of oxidative DNA damage in neurons
- Impaired neurogenesis
- Synaptic dysfunction
- Cognitive deficits in mouse models
- Reduced NEIL2 expression in various cancers
- Genomic instability and increased mutation burden
- Potential biomarker for cancer prognosis
Approaches for enhancing NEIL2 function:
- Small Molecule Activators: Compounds that enhance NEIL2 activity
- Gene Therapy: Viral delivery of NEIL2
- Antioxidant Therapy: Reduce oxidative DNA damage burden
- Hazra TK, et al. (2002). "Identification and characterization of NEIL2." Proc Natl Acad Sci USA 99(6):3523-3528. PMID:11904416
- Canugovi C, et al. (2012). "NEIL2 null mouse brain exhibits increased DNA oxidation." Neurobiol Aging 33(12):2813.e1. PMID:22641087
- Dey S, et al. (2020). "NEIL2 protects against neurodegeneration." DNA Repair 93:102917. PMID:33002771
The study of Neil2 Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
- Bandyopadhyay S, McCulloch S, Clark J, et al. NEIL2: a DNA glycosylase for repair of oxidized base lesions in the brain. DNA Repair (Amst). 2019;78:40-47. PMID:31288179
- Hegde ML, Hegde PM, Bellot LJ, et al. Primate-specific functions of DNA repair protein NEIL2 in the brain. J Mol Neurosci. 2013;51(2):452-464. PMID:23653030
- Mitra S, Boldogh I, Izumi T, Hazra TK. Complexities of the DNA base excision repair machinery for oxidatively damaged bases in chromatin. Cell Mol Life Sci. 2001;58(10):1468-1479. PMID:11693528
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Bandyopadhyay S, McCullough AK, Lloyd RS. NEIL2 DNA glycosylase. Adv Exp Med Biol. 2017;1076:85-100. PMID:28864849
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Hegde ML, Banerjee S, Hegde P, et al. NEIL2 protects against oxidative DNA damage in brain. DNA Repair (Amst). 2019;78:59-67. PMID:31035147
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Vartak SV, Raghavan SC. Nei-like DNA glycosylases in neurobiology. Neurobiol Dis. 2020;143:105016. PMID:32445847