GO:0045007 depurination: DNA Damage Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0045007 depurination is the disruption of the bond between the sugar in the backbone and the A or G base, causing the base to be removed and leaving a depurinated sugar.
• Depurination generates abasic (AP) sites that are mutagenic and are a major source of spontaneous DNA damage.
• Site-specific self-catalyzed depurination can be biologically programmed and creates sequence diversity.
• Depurination is also a mechanism of ribosome inactivation by toxins such as ricin and colibactin-derived cross-links.
• Polyamines protect nucleic acids against depurination, linking cellular metabolism to DNA stability.
• Click-code-seq reveals strand biases of DNA oxidation and depurination in the human genome.
Description
Depurination (GO:0045007) is a fundamental biological process in which the N-glycosidic bond linking the sugar in the backbone to an adenine (A) or guanine (G) base is disrupted, causing the base to be removed and leaving a depurinated sugar (an abasic site). This process is a major source of spontaneous DNA damage and is a key driver of mutations and sequence diversity. Understanding depurination is essential because it impacts genome stability, aging, and the efficacy of certain anticancer drugs.
depurination At A Glance
| GO ID | GO:0045007 |
|---|---|
| GO term | depurination |
| Ontology | biological_process |
| Synonym | none |
| Major function | Removal of adenine or guanine bases from DNA or RNA, generating abasic sites |
| Related processes | DNA damage, mutagenesis, ribosome inactivation |
| Key enzymes/toxins | Ricin, colibactin, polyamines |
| Detection methods | Click-code-seq, comet assay, Ribo-seq |
What Is GO:0045007?
Depurination is the disruption of the bond between the sugar in the backbone and the A or G base, causing the base to be removed and leaving a depurinated sugar (an apurinic site).
Why Is depurination Important in Cell Biology?
Depurination is a constant threat to genome integrity, occurring spontaneously and through enzymatic or toxin-mediated mechanisms. It leads to mutations, strand breaks, and can trigger cell death or cancer. In RNA, depurination of the sarcin/ricin loop inhibits translation and activates stress responses. Thus, depurination is central to understanding mutagenesis, host-pathogen interactions, and the development of therapeutic strategies.
• Depurination is a major source of spontaneous DNA mutations and is linked to cancer and aging.
• It generates abasic sites that are cytotoxic and mutagenic if unrepaired.
• Ricin and other ribosome-inactivating proteins depurinate rRNA, inhibiting protein synthesis.
• Colibactin, a bacterial genotoxin, forms interstrand cross-links that undergo depurination, contributing to colorectal cancer.
• Polyamines protect nucleic acids against depurination, linking metabolism to genome stability.
• Depurination is a key damage type in ancient DNA, affecting phylogenetic analyses.
• Strand biases of depurination in the human genome have been revealed by click-code-seq.
• Site-specific self-catalyzed depurination creates sequence diversity and may drive evolution.
• Depurination of sarcin/ricin loop rRNA signals through the small ribosomal subunit during translation.
• Understanding depurination aids in designing stable nucleic acid therapeutics and diagnostics.
What Happens During depurination?
Initiation: N-glycosidic bond cleavage
In simple terms: The bond holding the base to the sugar breaks, leaving the base off.
Depurination begins with the hydrolysis of the N-glycosidic bond between the deoxyribose (or ribose) sugar and the adenine or guanine base, resulting in an abasic site. This can occur spontaneously or be catalyzed by enzymes or toxins.
Enzymatic and toxin-mediated depurination
In simple terms: Some proteins and toxins actively remove bases from DNA or RNA.
Ricin and other ribosome-inactivating proteins depurinate a specific adenine in the sarcin/ricin loop of 28S rRNA, inhibiting translation. Colibactin-derived interstrand cross-links undergo depurination, contributing to DNA damage.
Abasic site formation and processing
In simple terms: The missing base leaves a hole that can be repaired or cause mutations.
The resulting apurinic site is a substrate for base excision repair (BER) or can lead to mutations if bypassed by translesion synthesis. Depurination of sarcin/ricin loop rRNA is signaled through the small ribosomal subunit during translation.
Biological consequences: mutagenesis and sequence diversity
In simple terms: Depurination can change DNA sequences and create diversity.
Site-specific self-catalyzed DNA depurination leads to mutations and creates sequence diversity. The mutational specificity of depurination has been demonstrated in vitro and in vivo.
Protection and regulation by polyamines
In simple terms: Polyamines help protect DNA and RNA from losing bases.
Polyamines protect nucleic acids against depurination, suggesting a regulatory role in maintaining genome stability.
Key Genes Involved in GO:0045007 depurination
The following genes and proteins are involved in or affected by depurination, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| Ricin | Depurinates 28S rRNA | Ribosome inactivation, toxin research |
| Colibactin | Forms interstrand cross-links that depurinate | Colorectal cancer, genotoxicity |
| APEX1 | Repairs abasic sites | Base excision repair, mutagenesis |
| POLB | Polymerase in BER | Repair of depurinated sites |
| XRCC1 | Scaffold in BER | Repair of depurinated sites |
| HAC1 | ER stress-induced transcription factor | Ricin depurination inhibits HAC1 splicing |
| RPL | Ribosomal proteins | Sarcin/ricin loop depurination signaling |
| RPS | Ribosomal proteins | Sarcin/ricin loop depurination signaling |
| OGG1 | Oxidative damage repair | Depurination strand biases |
| MUTYH | Repairs oxidative damage | Depurination strand biases |
| TP53 | Tumor suppressor | Mutations from depurination |
| KRAS | Oncogene | Mutations from depurination |
| POLH | Translesion synthesis | Bypass of abasic sites |
| REV1 | Translesion synthesis | Bypass of abasic sites |
| SMUG1 | Base excision repair | Repair of depurinated sites |
| UNG | Uracil-DNA glycosylase | Related to depurination repair |
| APE1 | Apurinic endonuclease | Repair of abasic sites |
How Is depurination Regulated?
Depurination is regulated by cellular polyamines, which protect nucleic acids against depurination. Additionally, the process is influenced by oxidative stress and strand biases in the genome. Ricin-induced depurination of rRNA leads to inhibition of endoplasmic reticulum stress-induced HAC1 mRNA splicing on the ribosome, indicating a regulatory link between depurination and stress responses.
depurination and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| Colibactin | Colorectal cancer | Knockout of colibactin synthesis genes in E. coli |
| Ricin | Ribosome inactivation, bioterrorism | Point mutation of sarcin/ricin loop rRNA |
| APEX1 | Cancer, neurodegeneration | Knockout in human cell lines |
| TP53 | Cancer | Knock-in of depurination-induced mutations |
| POLB | Cancer | Overexpression in repair-deficient cells |
Cancer
Depurination generates mutations that can activate oncogenes or inactivate tumor suppressors, contributing to cancer development. Colibactin-producing bacteria cause depurination of interstrand cross-links, leading to colorectal cancer.
Ribosomopathies and toxin-mediated diseases
Ricin depurination of 28S rRNA inhibits protein synthesis and triggers ribotoxic stress, relevant to ribosomopathies and bioterrorism. Depurination of sarcin/ricin loop rRNA is signaled through the small ribosomal subunit during translation.
Neurodegeneration and aging
Accumulation of depurination-induced DNA damage is linked to aging and neurodegenerative diseases, though specific mechanisms require further study.
From depurination-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X repair depurination? | Knockout of X in HEK293T cells |
| Does mutation Y affect depurination? | Point mutation knock-in of Y |
| Can we tag depurination sites? | Tagged knock-in of APEX1 |
| Does overexpression of Z protect against depurination? | Overexpression of Z in HeLa cells |
| What is the strand bias of depurination? | Click-code-seq in human cells |
| Does polyamine depletion increase depurination? | Knockout of polyamine synthesis genes |
How to Study the depurination Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Click-code-seq | Strand biases of depurination | Genome-wide mapping |
| Ribo-seq | Ribosome depurination | Translation studies |
| Comet assay | DNA strand breaks | Genotoxicity testing |
| Mass spectrometry | Depurination adducts | Colibactin research |
| qPCR | Abasic site quantification | Repair studies |
| Western blot | Repair protein levels | BER pathway |
| Immunofluorescence | AP site localization | Cell biology |
Click-code-seq
Click-code-seq reveals strand biases of DNA oxidation and depurination in the human genome.
Ribo-seq
Ribo-seq can detect depurination of sarcin/ricin loop rRNA and its signaling through the small ribosomal subunit.
Comet assay
The comet assay measures DNA strand breaks resulting from depurination and repair intermediates.
Mass spectrometry
Mass spectrometry can quantify depurination adducts and cross-links.
How CRISPR Can Be Used to Study GO:0045007 depurination
Knockout
CRISPR knockout of repair genes such as APEX1 or POLB can sensitize cells to depurination and reveal repair mechanisms.
Point Mutation
Point mutation knock-in of specific residues in ricin or colibactin can abolish depurination activity and test function.
Knock-in
Knock-in of tagged APEX1 allows visualization of abasic site repair in live cells.
Overexpression
Overexpression of polyamine synthesis genes can protect against depurination and test protective mechanisms.
How EDITGENE Supports depurination Research
Researchers studying depurination-related genes often need to determine whether a candidate gene is causally involved in DNA damage repair, ribosome inactivation, or mutagenesis. EDITGENE provides CRISPR services to create precise cellular models for such studies.
Contact EDITGENE today to design your custom CRISPR model for depurination research.
Frequently Asked Questions About depurination
What is depurination?
Depurination is the disruption of the bond between the sugar in the backbone and the A or G base, causing the base to be removed and leaving a depurinated sugar.
What genes are involved in depurination?
Genes such as APEX1, POLB, XRCC1, and TP53 are involved in repair or response to depurination.
How does depurination cause mutations?
Depurination generates abasic sites that can be bypassed by translesion synthesis, leading to mutations.
What is the role of ricin in depurination?
Ricin depurinates a specific adenine in the sarcin/ricin loop of 28S rRNA, inhibiting translation.
Can depurination be detected?
Yes, methods like click-code-seq, comet assay, and mass spectrometry can detect depurination.
What is the GO ID for depurination?
The GO ID for depurination is GO:0045007.
How do polyamines affect depurination?
Polyamines protect nucleic acids against depurination.
Is depurination linked to cancer?
Yes, depurination-induced mutations can contribute to cancer, and colibactin depurination is linked to colorectal cancer.
What is the sarcin/ricin loop?
The sarcin/ricin loop is a conserved rRNA structure that can be depurinated by ricin, leading to translation inhibition.
How can CRISPR help study depurination?
CRISPR can create knockout, point mutation, and knock-in models to study genes involved in depurination repair and response.
Conclusion
Depurination (GO:0045007) is a critical biological process with wide-ranging implications for genome stability, mutagenesis, and disease. Understanding its mechanisms and regulation is essential for developing therapeutic strategies. EDITGENE offers comprehensive CRISPR services to facilitate research in this field.
References
- 1. Xue M et al.. 2020. Depurination of Colibactin-Derived Interstrand Cross-Links.. Biochemistry 59(7):892-900 PMID: 31977191
- 2. Prashar T et al.. 2025. Depurination of sarcin/ricin loop 25S rRNA is signaled through the small ribosomal subunit during translation.. RNA 31(12):1812-1825 PMID: 40987586
- 3. Fresco JR et al.. 2017. Site-Specific Self-Catalyzed DNA Depurination: A Biological Mechanism That Leads to Mutations and Creates Sequence Diversity.. Annu Rev Biochem 86:461-484 PMID: 28654322
- 4. Terui Y et al.. 2018. Polyamines protect nucleic acids against depurination.. Int J Biochem Cell Biol 99:147-153 PMID: 29649565
- 5. Pierce M et al.. 2019. Ribosome depurination by ricin leads to inhibition of endoplasmic reticulum stress-induced HAC1 mRNA splicing on the ribosome.. J Biol Chem 294(47):17848-17862 PMID: 31624149
- 6. Dabney J et al.. 2013. Ancient DNA damage.. Cold Spring Harb Perspect Biol 5(7) PMID: 23729639
- 7. Takhaveev V et al.. 2026. Click-code-seq reveals strand biases of DNA oxidation and depurination in human genome.. Nat Chem Biol 22(5):716-727 PMID: 41174235
- 8. Kunkel TA. 1984. Mutational specificity of depurination.. Proc Natl Acad Sci U S A 81(5):1494-8 PMID: 6369329
