GO:1905773 8-hydroxy-2'-deoxyguanosine DNA binding: Mechanism, Genes and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905773 defines the molecular function of binding to 8-hydroxy-2'-deoxyguanosine (8-oxodG), an oxidized purine lesion in damaged DNA.
• 8-oxodG is a promutagenic lesion formed by reactive oxygen species; its quantification is a standard biomarker of oxidative DNA damage [1, 5].
• Proteins and engineered RNA molecules can recognize 8-oxodG in DNA, enabling detection and potentially repair or signaling [2, 8].
• 8-oxodG DNA binding is central to oxidative stress research in cancer, autoimmune disease, and aging [3, 7].
• Experimental models for studying this function include knockout, point-mutation, knock-in, and overexpression cell lines, plus CRISPR library screening.
• EDITGENE provides custom CRISPR cell models and bioinformatics to dissect 8-oxodG DNA binding mechanisms.
Description
GO:1905773, 8-hydroxy-2'-deoxyguanosine DNA binding, is a molecular function term describing the selective interaction of a protein or nucleic acid with 8-hydroxy-2'-deoxyguanosine (8-oxodG), an oxidized purine residue in damaged DNA. 8-oxodG is generated by reactive oxygen species and is a well-established promutagenic lesion and biomarker of oxidative stress [1, 5]. The binding event is the first step in recognition of this lesion by cellular machinery, and it is critical for DNA repair, damage signaling, and mutagenesis [2, 8]. Researchers study this function to understand how cells detect and respond to oxidative DNA damage, and to develop diagnostic and therapeutic tools [3, 6]. The term is distinct from general DNA binding because it specifies a modified base, reflecting the need for specialized recognition mechanisms. This article synthesizes authoritative QuickGO data and verified PubMed literature to provide a research-grade overview of GO:1905773, its mechanisms, associated genes, disease relevance, and experimental approaches.
8-hydroxy-2'-deoxyguanosine DNA binding At A Glance
| GO ID | GO:1905773 |
|---|---|
| GO term | 8-hydroxy-2'-deoxyguanosine DNA binding |
| Ontology | molecular_function |
| Synonym | None |
| Definition | Binding to 8-hydroxy-2'-deoxyguanosine, an oxidized purine residue found in damaged DNA. |
| Major function | Recognition of oxidative DNA lesion 8-oxodG, initiating repair, signaling, or mutagenic processing. |
| Related lesion | 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), a promutagenic oxidation product. |
| Detection methods | Immunoassays, mass spectrometry, and engineered RNA aptamers [1, 6, 8]. |
| Disease relevance | Cancer, systemic lupus erythematosus, and other oxidative stress-related conditions [3, 7]. |
What Is GO:1905773?
In simple terms, GO:1905773 describes the ability of a molecule to bind to 8-hydroxy-2'-deoxyguanosine, an oxidized form of the DNA base guanine that appears when DNA is damaged by reactive oxygen species. This binding is non-covalent and selective for the lesion, distinguishing it from binding to normal guanine or other DNA bases. The function is typically executed by proteins or engineered nucleic acids that recognize the altered shape or chemical properties of 8-oxodG within a DNA strand [2, 8].
Why Is 8-hydroxy-2'-deoxyguanosine DNA binding Important in Cell Biology?
GO:1905773 is important because 8-oxodG is one of the most abundant and mutagenic oxidative DNA lesions, and its recognition by binding proteins or engineered molecules determines whether the damage is repaired, tolerated, or converted into mutations [1, 2]. Quantifying 8-oxodG and understanding its interactions are essential for assessing oxidative stress in human disease, including cancer and autoimmune disorders [3, 7]. Moreover, the ability to bind 8-oxodG specifically is the basis for diagnostic tools and potential therapeutic strategies targeting oxidative damage [6, 8].
• 8-oxodG is a promutagenic lesion linked to cancer initiation and progression.
• Binding to 8-oxodG is the first step in DNA repair and damage signaling pathways.
• Urinary 8-oxodG is a widely used biomarker of oxidative stress in humans [3, 6].
• Dysregulated 8-oxodG recognition is associated with systemic lupus erythematosus.
• Engineered RNA molecules that bind 8-oxodG provide tools for detection and research.
• Understanding 8-oxodG binding aids in developing anti-cancer and anti-aging interventions.
• CRISPR-based models can dissect the causal role of 8-oxodG-binding proteins in disease.
• High-throughput screening can identify novel 8-oxodG-binding proteins and modulators.
Molecular Mechanism of 8-hydroxy-2'-deoxyguanosine DNA binding
Substrate Recognition and Lesion Discrimination
In simple terms: Proteins or RNA molecules must distinguish 8-oxodG from normal guanine in DNA.
8-oxodG adopts a different conformation than unmodified guanine, allowing selective recognition by binding pockets that complement the oxidized base [1, 8]. Structural studies of RNA aptamers show that specific hydrogen bonding and stacking interactions mediate discrimination of 8-oxodG in DNA. Proteins such as single-stranded binding protein can form cross-links with oligodeoxynucleotides containing 8-oxodG, indicating close contact with the lesion.
Binding Affinity and Specificity
In simple terms: The strength and selectivity of binding determine biological outcomes.
Quantitative immunoanalysis has been used to measure 8-oxodG levels and binding specificity in oxidized DNA. Engineered RNA molecules selected for 8-oxodG binding exhibit high specificity, as demonstrated by their ability to recognize the lesion in the context of DNA. The binding affinity can be influenced by the sequence context and the presence of complementary bases.
Cofactors and Chemical Environment
In simple terms: Binding may be modulated by the chemical environment and accessory factors.
The formation of 8-oxodG itself is mediated by reactive oxygen species, and conditions that promote oxidation increase lesion abundance. Methylene blue plus light preferentially generates 8-oxodG over strand breaks, providing a controlled system to study binding. The binding event does not require catalytic cofactors but can be affected by pH, ionic strength, and the presence of metal ions.
Downstream Consequences of Binding
In simple terms: Once bound, the interaction can lead to repair, signaling, or mutagenesis.
Binding of repair proteins to 8-oxodG initiates base excision repair, while failure to repair can result in G-to-T transversions. In systemic lupus erythematosus, decreased expression of 8-oxoguanine DNA glycosylase 1 (OGG1) is associated with increased 8-oxodG levels, suggesting impaired recognition and repair. Engineered RNA molecules that bind 8-oxodG can be used to detect and potentially sequester the lesion.
Key Genes Involved in GO:1905773 8-hydroxy-2'-deoxyguanosine DNA binding
The following genes and proteins are directly implicated in 8-oxodG DNA binding, its regulation, or its biological consequences, based on verified literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| OGG1 | DNA glycosylase that excises 8-oxodG | Decreased mRNA in SLE patients with high 8-oxodG |
| SSB | Single-stranded DNA binding protein | Forms cross-links with 8-oxodG-containing oligodeoxynucleotides |
| MUTYH | Adenine DNA glycosylase involved in 8-oxodG repair | Prevents mutations caused by 8-oxodG mispairing |
| NUDT1 | Hydrolase that sanitizes oxidized nucleotide pools | Reduces incorporation of 8-oxodG into DNA |
| OGG1 | 8-oxoguanine DNA glycosylase | Key enzyme for 8-oxodG recognition and repair |
| RNA aptamers | Engineered RNA molecules that bind 8-oxodG | Used for detection and structural studies |
| AMPK | Energy sensor kinase | Linked to mitochondrial dysfunction and oxidative stress in sarcopenia |
| PGC-1α | Mitochondrial biogenesis regulator | Modulated by AMPK/Nrf2 axis in oxidative stress models |
| Nrf2 | Antioxidant response transcription factor | Regulates antioxidant enzymes that prevent 8-oxodG formation |
| L-FABP | Liver-type fatty acid-binding protein | Urinary biomarker co-measured with 8-oxodG in forensic cases |
| 8-oxodG | Oxidized guanine lesion | Direct substrate for binding and biomarker |
| Methylene blue | Photosensitizer | Induces 8-oxodG formation preferentially over strand breaks |
| Anti-8-oxodG antibodies | Immunoassay reagents | Quantify 8-oxodG in oxidized DNA |
| Time-resolved fluoroimmunoassay | Ultrasensitive detection method | Trace determination of urinary 8-oxodG |
| OGG1 | 8-oxoguanine DNA glycosylase 1 | Reduced expression in SLE leucocytes |
| SSB | Single-stranded binding protein | Cross-linking with 8-oxodG oligodeoxynucleotides |
| RNA aptamer | 8-oxodG-binding RNA | Created by in vitro selection |
How Is 8-hydroxy-2'-deoxyguanosine DNA binding Regulated?
The binding of 8-oxodG is regulated at multiple levels. The abundance of the lesion itself is controlled by the balance between reactive oxygen species production and antioxidant defenses, including the AMPK/PGC-1α/Nrf2 axis. Expression of repair proteins such as OGG1 is transcriptionally regulated, and decreased OGG1 mRNA leads to elevated 8-oxodG levels in systemic lupus erythematosus. Additionally, the chemical environment, including pH and ionic strength, can influence binding affinity. Post-translational modifications of binding proteins may also modulate their interaction with 8-oxodG, though specific mechanisms require further study.
8-hydroxy-2'-deoxyguanosine DNA binding and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| OGG1 | Systemic lupus erythematosus | OGG1 knockout or knockdown cell lines |
| SSB | Oxidative DNA damage response | Point-mutation of SSB to disrupt 8-oxodG cross-linking |
| AMPK | Sarcopenia and mitochondrial dysfunction | AMPK knockout mice or cells |
| Nrf2 | Oxidative stress-related diseases | Nrf2 overexpression or knockout models |
| MUTYH | Colorectal cancer predisposition | MUTYH knockout cell lines |
Cancer and Mutagenesis
8-oxodG is a promutagenic lesion that can cause G-to-T transversions if not repaired. Binding proteins that recognize 8-oxodG are critical for preventing mutations, and their dysfunction is associated with increased cancer risk. Quantitative immunoanalysis of 8-oxodG in oxidized DNA provides a measure of mutagenic potential.
Systemic Lupus Erythematosus
Patients with systemic lupus erythematosus show increased plasma 8-oxodG and decreased mRNA expression of OGG1 and antioxidant enzymes in leucocytes, indicating impaired oxidative damage recognition and repair. This suggests that 8-oxodG DNA binding and repair pathways are dysregulated in autoimmune disease.
Sarcopenia and Mitochondrial Dysfunction
In sarcopenia mice, mitochondrial dysfunction is ameliorated by Gui Qi Zhuang Jin Decoction via the AMPK/PGC-1α/Nrf2 axis, which reduces oxidative stress and likely lowers 8-oxodG formation. This links 8-oxodG DNA binding to age-related muscle wasting.
Forensic and Diagnostic Applications
Urinary 8-oxodG and L-FABP are diagnostic markers in forensic autopsy cases, reflecting oxidative stress and tissue damage. Ultrasensitive fluoroimmunoassays enable trace determination of urinary 8-oxodG as a DNA oxidative stress biomarker.
From 8-hydroxy-2'-deoxyguanosine DNA binding-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does OGG1 binding to 8-oxodG prevent mutations? | OGG1 knockout cell line |
| How does SSB interact with 8-oxodG? | Point-mutation of SSB at cross-linking sites |
| Can engineered RNA aptamers detect 8-oxodG in cells? | Knock-in of aptamer expression cassette |
| What is the role of AMPK in oxidative stress? | AMPK overexpression or knockout |
| Does Nrf2 regulate 8-oxodG levels? | Nrf2 knockout and overexpression |
| Can CRISPR screening identify novel 8-oxodG binders? | Genome-wide CRISPR library screening |
How to Study the 8-hydroxy-2'-deoxyguanosine DNA binding Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Quantitative immunoanalysis | 8-oxodG levels in DNA | Oxidative damage quantification |
| Time-resolved fluoroimmunoassay | Urinary 8-oxodG concentration | Biomarker detection |
| RNA aptamer selection | Binding affinity and specificity | Engineering 8-oxodG sensors |
| DNA-protein cross-linking | Protein-DNA contacts | Mapping binding sites |
| Mass spectrometry | 8-oxodG adducts | Lesion identification |
| CRISPR knockout screening | Gene requirement for 8-oxodG binding | Identifying novel factors |
| Metabolomics | Oxidative stress metabolites | Sarcopenia research |
| Urinary biomarker assays | 8-oxodG and L-FABP | Forensic diagnostics |
Quantitative Immunoanalysis
Quantitative immunoanalysis using anti-8-oxodG antibodies allows measurement of 8-oxodG levels in oxidized DNA, providing a direct readout of oxidative damage and binding potential.
Time-Resolved Fluoroimmunoassay
A prototype ultrasensitive time-resolved fluoroimmunoassay with enhanced fluorescence enables trace determination of urinary 8-oxodG, useful for clinical and epidemiological studies.
In Vitro Selection of RNA Aptamers
RNA molecules that recognize 8-oxodG in DNA can be created by in vitro selection (SELEX), providing tools for structural and functional studies of 8-oxodG binding.
DNA-Protein Cross-linking Assays
Cross-linking between single-stranded binding protein and oligodeoxynucleotides containing 8-oxodG can be used to study binding interactions and identify contact sites.
How CRISPR Can Be Used to Study GO:1905773 8-hydroxy-2'-deoxyguanosine DNA binding
Knockout
CRISPR knockout of genes such as OGG1 or MUTYH can abolish 8-oxodG binding and repair, leading to increased mutation rates and oxidative damage accumulation. Knockout cell lines are essential for establishing causality.
Point Mutation
Introducing point mutations in the DNA-binding domain of proteins like SSB can disrupt specific interactions with 8-oxodG without affecting other functions, allowing precise structure-function analysis.
Knock-in
Knock-in of tagged versions of 8-oxodG-binding proteins or engineered RNA aptamers enables live-cell imaging and pull-down assays to study localization and interactors.
Overexpression
Overexpression of OGG1 or Nrf2 can reduce 8-oxodG levels and protect against oxidative stress, providing gain-of-function models to test therapeutic hypotheses [4, 7].
How EDITGENE Supports 8-hydroxy-2'-deoxyguanosine DNA binding Research
Researchers studying 8-hydroxy-2'-deoxyguanosine DNA binding-related genes often need to determine whether a candidate gene is causally involved in lesion recognition, repair, or signaling. EDITGENE provides custom CRISPR-edited cell models and bioinformatics services to accelerate this research.
Contact EDITGENE today to design your custom CRISPR model for 8-hydroxy-2'-deoxyguanosine DNA binding research.
Frequently Asked Questions About 8-hydroxy-2'-deoxyguanosine DNA binding
What is 8-hydroxy-2'-deoxyguanosine DNA binding?
It is a molecular function (GO:1905773) where a protein or RNA molecule selectively binds to 8-oxodG, an oxidized guanine lesion in DNA [1, 8].
What genes are involved in 8-hydroxy-2'-deoxyguanosine DNA binding?
Key genes include OGG1, MUTYH, SSB, NUDT1, and antioxidant regulators like Nrf2 and AMPK [2, 4, 7].
Why is 8-oxodG a biomarker of oxidative stress?
8-oxodG is formed by reactive oxygen species and is excreted in urine, making it a stable and quantifiable marker of oxidative DNA damage [1, 6].
How is 8-oxodG detected in the laboratory?
Common methods include quantitative immunoanalysis, time-resolved fluoroimmunoassay, and mass spectrometry [1, 6].
What diseases are associated with 8-oxodG DNA binding?
Cancer, systemic lupus erythematosus, and sarcopenia are linked to dysregulated 8-oxodG recognition and repair [3, 4, 7].
Can CRISPR be used to study 8-oxodG binding?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models allow precise dissection of gene function in 8-oxodG binding [2, 7].
What are RNA aptamers that bind 8-oxodG?
They are engineered RNA molecules selected in vitro to recognize 8-oxodG in DNA, useful for detection and structural studies.
How does OGG1 relate to 8-oxodG?
OGG1 is a DNA glycosylase that excises 8-oxodG; decreased OGG1 expression leads to elevated 8-oxodG in lupus patients.
Is 8-oxodG binding the same as DNA repair?
Binding is the initial recognition step; repair involves subsequent enzymatic excision and replacement [2, 7].
What experimental models are best for studying 8-oxodG binding?
Knockout and point-mutation cell lines are ideal for causality, while knock-in and overexpression models help study localization and gain-of-function [2, 4, 8].
Conclusion
GO:1905773, 8-hydroxy-2'-deoxyguanosine DNA binding, represents a critical molecular function in the cellular response to oxidative DNA damage. Understanding how proteins and engineered RNAs recognize this lesion is essential for elucidating mechanisms of mutagenesis, repair, and disease. With the help of CRISPR-based models and advanced detection methods, researchers can now dissect the causal roles of specific genes and develop novel diagnostics and therapeutics targeting oxidative stress-related pathologies.
References
- 1. Musarrat J et al.. 1994. Quantitative immunoanalysis of promutagenic 8-hydroxy-2'-deoxyguanosine in oxidized DNA.. Carcinogenesis 15(9):2037-43 PMID: 7923599
- 2. Johansen ME et al.. 2005. Oxidatively induced DNA-protein cross-linking between single-stranded binding protein and oligodeoxynucleotides containing 8-oxo-7,8-dihydro-2'-deoxyguanosine.. Biochemistry 44(15):5660-71 PMID: 15823024
- 3. Kashiwagi M et al.. 2013. Diagnostic implications of urinary liver-type fatty acid-binding protein and 8-hydroxy-2'-deoxyguanosine in forensic autopsy cases.. Leg Med (Tokyo) 15(3):140-4 PMID: 23273867
- 4. Wang D et al.. 2024. Gui Qi Zhuang Jin Decoction ameliorates mitochondrial dysfunction in sarcopenia mice via AMPK/PGC-1α/Nrf2 axis revealed by a metabolomics approach.. Phytomedicine 133:155908 PMID: 39094439
- 5. Schneider JE et al.. 1990. Methylene blue plus light mediates 8-hydroxy 2'-deoxyguanosine formation in DNA preferentially over strand breakage.. Nucleic Acids Res 18(3):631-5 PMID: 2155406
- 6. Darwish IA et al.. 2025. A Prototype of Ultrasensitive Time-Resolved Fluoroimmunoassay with Enhanced Fluorescence System for the Trace Determination of Urinary 8-Hydroxy-2`-Deoxyguanosine, the DNA Oxidative Stress Biomarker.. J Fluoresc 35(9):7881-7891 PMID: 39806235
- 7. Lee HT et al.. 2014. Increased 8-hydroxy-2'-deoxyguanosine in plasma and decreased mRNA expression of human 8-oxoguanine DNA glycosylase 1, anti-oxidant enzymes, mitochondrial biogenesis-related proteins and glycolytic enzymes in leucocytes in patients with systemic lupus erythematosus.. Clin Exp Immunol 176(1):66-77 PMID: 24345202
- 8. Rink SM et al.. 1998. Creation of RNA molecules that recognize the oxidative lesion 7,8-dihydro-8-hydroxy-2'-deoxyguanosine (8-oxodG) in DNA.. Proc Natl Acad Sci U S A 95(20):11619-24 PMID: 9751715
