GO:1905051 regulation of base-excision repair: Regulatory Mechanisms, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:1905051 (regulation of base-excision repair) is a biological_process term defined as any process that modulates the frequency, rate or extent of base-excision repair (BER).
• BER is the primary DNA repair pathway for small, non-helix-distorting base lesions caused by oxidation, alkylation, deamination and hydrolysis.
• Regulation of BER occurs at multiple levels, including post-translational modification (ubiquitylation, acetylation), NAD+-dependent signaling, and transcriptional control of BER genes.
• Dysregulation of BER regulation is implicated in cancer, neurodegeneration and metabolic disease, making it a major therapeutic and biomarker target.
• Key regulatory nodes include OGG1, APE1, XRCC1, PARP1, SIRT1/SIRT6, and the ubiquitin-proteasome system.
• CRISPR knockout, point-mutation, knock-in and overexpression models are essential for dissecting causal roles of BER regulatory genes in disease.
Description
Base-excision repair (BER) is the major DNA repair pathway that removes small, non-helix-distorting base lesions generated by oxidation, alkylation, deamination and spontaneous hydrolysis. Because unrepaired lesions can cause mutations and cell death, the frequency and rate of BER must be tightly controlled. The Gene Ontology term GO:1905051, regulation of base-excision repair, captures any process that modulates the frequency, rate or extent of BER. This term is a biological_process and is often abbreviated as regulation of BER. Understanding how BER is regulated is critical because changes in BER capacity influence genome stability, cancer risk, and responses to genotoxic therapy. Research over the past decade has revealed that BER is not a constitutive, unregulated pathway; instead, it is fine-tuned by post-translational modifications, cofactor availability, and transcriptional programs. For example, NAD+-dependent enzymes such as PARP1 and sirtuins modulate BER activity in response to cellular energy status and DNA damage. Ubiquitylation and acetylation of BER proteins control their stability, localization and catalytic activity. Transcriptional dysregulation of BER genes has been documented in breast cancer and hepatocellular carcinoma, linking regulation of BER to tumor progression. This article provides a research-grade overview of GO:1905051, covering its definition, mechanistic stages, key genes, disease relevance, and experimental methods including CRISPR-based models. All statements are grounded in published literature cited by number.
regulation of base-excision repair At A Glance
| GO ID | GO:1905051 |
|---|---|
| GO term | regulation of base-excision repair |
| Ontology | biological_process |
| Synonym | regulation of BER |
| Definition | Any process that modulates the frequency, rate or extent of base-excision repair. |
| Major function | Controls the rate and extent of DNA base lesion removal by BER. |
| Related processes | Base-excision repair (GO:0006284), DNA damage response, single-strand break repair. |
| Key regulatory mechanisms | Ubiquitylation, acetylation, NAD+-dependent signaling, transcriptional control. |
| Disease relevance | Cancer, neurodegeneration, metabolic and inflammatory diseases. |
What Is GO:1905051?
GO:1905051, regulation of base-excision repair, is defined by QuickGO as any process that modulates the frequency, rate or extent of base-excision repair. In other words, it encompasses all molecular and cellular events that change how often, how fast, or how completely BER removes damaged bases from DNA. This includes direct modulation of BER enzyme activity, changes in BER protein abundance or localization, and signaling events that alter BER capacity in response to cellular conditions.
Why Is regulation of base-excision repair Important in Cell Biology?
Regulation of base-excision repair is important because BER is a double-edged sword: insufficient BER leads to mutation accumulation and genomic instability, while excessive or misregulated BER can cause futile repair cycles, apoptosis, or resistance to DNA-damaging therapies. Understanding GO:1905051 helps researchers identify regulatory nodes that can be targeted to sensitize tumors to chemotherapy or protect normal tissues from oxidative damage.
• BER is the main pathway for repairing oxidative and alkylation base damage, and its regulation determines mutation load.
• Dysregulated BER regulation is associated with breast cancer, hepatocellular carcinoma and other malignancies.
• NAD+-dependent regulation links BER capacity to cellular metabolism and aging.
• Ubiquitylation and acetylation of BER proteins provide reversible switches for repair activity.
• Transcriptional control of BER genes affects tumor progression and therapy response.
• Single-strand break repair, which is closely related to BER, is defective in human genetic diseases.
• Regulation of BER influences the efficacy of alkylating agents and radiation therapy.
• BER regulatory proteins are potential biomarkers and drug targets.
• CRISPR models enable causal testing of BER regulatory genes.
• Understanding BER regulation aids in predicting individual responses to genotoxic exposure.
What Happens During regulation of base-excision repair?
Initiation and damage recognition
In simple terms: The cell first finds the damaged DNA base and starts the repair process.
BER is initiated by DNA glycosylases that recognize and remove specific damaged bases, creating an abasic (AP) site. Regulation at this stage can occur through changes in glycosylase expression, stability, or activity. For example, OGG1, the main glycosylase for 8-oxoguanine, is regulated at the mRNA level by RNA-binding proteins such as RBM39 in hepatocellular carcinoma. Ubiquitylation of glycosylases can alter their turnover and recruitment to damage sites.
AP site processing and strand incision
In simple terms: The abasic site is cut to create a break that can be repaired.
AP endonuclease 1 (APE1) cleaves the AP site, generating a single-strand break with 5'-deoxyribose phosphate and 3'-hydroxyl ends. APE1 activity and localization are regulated by post-translational modifications, including acetylation and ubiquitylation. NAD+-dependent signaling can also influence APE1 function indirectly through PARP1 activation.
Gap filling and ligation
In simple terms: The missing DNA base is replaced and the DNA backbone is sealed.
DNA polymerase beta fills the single-nucleotide gap, and XRCC1-LIG3 or LIG1 seals the nick. Regulation of this step involves ubiquitylation of XRCC1 and other scaffold proteins, which affects their assembly into repair complexes. Acetylation of polymerase beta and other BER factors can modulate their catalytic efficiency. Single-strand break repair, which shares factors with BER, is also regulated by these modifications.
NAD+-dependent regulation
In simple terms: Cellular energy status can tune how fast BER works.
NAD+ serves as a substrate for PARP1 and sirtuins, which regulate BER in response to metabolic stress. PARP1 activation at damage sites promotes repair complex assembly, while sirtuins can deacetylate BER proteins to alter their activity. This links regulation of BER to cellular metabolism and aging.
Transcriptional and post-transcriptional control
In simple terms: The cell can make more or less of the repair proteins as needed.
Transcriptional dysregulation of BER genes has been observed in breast cancer, where altered expression of multiple BER factors contributes to genomic instability. In hepatocellular carcinoma, RBM39 stabilizes OGG1 mRNA to promote BER and tumor progression. These examples show that regulation of BER occurs at the level of gene expression and mRNA stability.
Key Genes Involved in GO:1905051 regulation of base-excision repair
The following genes and proteins are central to the regulation of base-excision repair, based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| OGG1 | 8-oxoguanine DNA glycosylase; initiates BER for oxidative damage | Regulated by RBM39 in HCC; target for cancer studies |
| APE1 | AP endonuclease; cleaves AP sites | Acetylation and ubiquitylation regulate its activity |
| XRCC1 | Scaffold protein; coordinates BER complex assembly | Ubiquitylation controls its stability and function |
| PARP1 | NAD+-dependent ADP-ribosyltransferase; regulates BER and SSBR | NAD+ signaling modulates BER capacity |
| POLB | DNA polymerase beta; fills gaps in BER | Acetylation affects its catalytic activity |
| LIG3 | DNA ligase III; seals nicks in BER | Part of XRCC1-LIG3 complex; regulated by ubiquitylation |
| LIG1 | DNA ligase I; alternative ligase in BER | Backup ligation; regulated by post-translational modifications |
| SIRT1 | NAD+-dependent deacetylase; regulates BER proteins | Links metabolism to BER regulation |
| SIRT6 | NAD+-dependent deacetylase; involved in BER and genome stability | Modulates BER under metabolic stress |
| RBM39 | RNA-binding protein; stabilizes OGG1 mRNA | Promotes BER in HCC; potential therapeutic target |
| MUTYH | DNA glycosylase; removes adenine mispaired with 8-oxoG | Mutations cause MUTYH-associated polyposis |
| NTHL1 | DNA glycosylase; removes oxidized pyrimidines | Biallelic mutations cause polyposis and cancer |
| NEIL1 | DNA glycosylase; removes oxidized bases | Regulated during oxidative stress |
| TDG | Thymine DNA glycosylase; removes deaminated bases | Regulated by ubiquitylation and acetylation |
| UNG | Uracil DNA glycosylase; removes uracil from DNA | Key BER initiator; regulated by post-translational modifications |
| FEN1 | Flap endonuclease; involved in long-patch BER | Regulated by acetylation and ubiquitylation |
| PCNA | Proliferating cell nuclear antigen; coordinates long-patch BER | Ubiquitylation regulates its function in BER |
| SMUG1 | Single-strand selective monofunctional uracil DNA glycosylase | Backup uracil removal; regulated by expression changes |
How Is regulation of base-excision repair Regulated?
Regulation of base-excision repair is itself regulated by multiple signaling inputs. NAD+-dependent enzymes, including PARP1 and sirtuins, sense cellular energy status and modulate BER activity. Ubiquitylation and acetylation of BER proteins provide reversible switches that control their stability, localization and catalytic activity. Transcriptional and post-transcriptional mechanisms, such as RBM39-mediated stabilization of OGG1 mRNA, adjust BER capacity in response to oncogenic stress. These layers of regulation ensure that BER is tuned to the cellular context and can be rapidly altered after DNA damage.
regulation of base-excision repair and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| OGG1 | Hepatocellular carcinoma; oxidative DNA damage | KO and overexpression in HCC cell lines |
| MUTYH | MUTYH-associated polyposis; colorectal cancer | Knock-in of patient mutations in colon cells |
| NTHL1 | NTHL1-associated polyposis; cancer predisposition | KO in intestinal organoids |
| XRCC1 | Breast cancer; genomic instability | Point mutation of ubiquitylation sites |
| RBM39 | HCC progression; OGG1 mRNA stability | KO and overexpression in liver cancer cells |
Cancer
Dysregulation of BER regulation is strongly linked to cancer. Transcriptional dysregulation of BER proteins has been reported in breast cancer, where altered expression of multiple BER genes contributes to genomic instability and tumor progression. In hepatocellular carcinoma, RBM39 promotes BER by stabilizing OGG1 mRNA, facilitating tumor progression. Germline mutations in MUTYH and NTHL1, which are BER glycosylases, cause inherited cancer predisposition syndromes. These findings highlight regulation of BER as a cancer-relevant process.
Neurodegeneration
Defective BER regulation is implicated in neurodegenerative diseases, where oxidative DNA damage accumulates in post-mitotic neurons. Single-strand break repair, which shares factors with BER, is defective in human genetic diseases such as ataxia with oculomotor apraxia and spinocerebellar ataxia. Regulation of BER capacity may influence neuronal survival under oxidative stress.
Metabolic and aging-related diseases
NAD+-mediated regulation of BER connects DNA repair to cellular metabolism and aging. Sirtuins and PARP1, which consume NAD+, modulate BER activity and are implicated in metabolic stress responses. This suggests that regulation of BER contributes to aging-related pathologies.
From regulation of base-excision repair-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of a BER regulatory gene increase mutation load? | CRISPR knockout cell lines |
| Does a specific post-translational modification site regulate BER activity? | Point-mutation knock-in of acetylation or ubiquitylation sites |
| Does a disease-associated variant alter BER capacity? | Knock-in of patient variants |
| Does overexpression of a BER regulator promote tumor progression? | Overexpression cell models |
| Where does a BER regulatory protein localize after damage? | Tagged knock-in with fluorescent tag |
| Which BER regulators are essential for survival? | Genome-wide CRISPR library screening |
How to Study the regulation of base-excision repair Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout | Loss-of-function effects on BER | Testing causal role of regulatory genes |
| Point-mutation knock-in | Effect of specific modification sites | Dissecting ubiquitylation/acetylation sites |
| Overexpression | Gain-of-function effects | Modeling oncogenic BER regulators |
| RNA-seq | Transcriptional changes in BER genes | Profiling dysregulation in cancer |
| Proteomics | Protein abundance and modifications | Identifying BER regulatory networks |
| Comet assay | DNA strand breaks and repair kinetics | Quantifying BER capacity |
| Fluorescence imaging | Subcellular localization and dynamics | Tracking repair complex assembly |
| CRISPR library screening | Genome-wide fitness and repair phenotypes | Identifying novel BER regulators |
CRISPR knockout and point-mutation models
CRISPR-Cas9 knockout of BER regulatory genes allows researchers to test their causal role in DNA repair and disease. Point-mutation knock-in can dissect specific post-translational modification sites, such as ubiquitylation or acetylation sites on XRCC1 or APE1.
Transcriptomic and proteomic profiling
RNA-seq and proteomics can reveal changes in BER gene expression and protein abundance upon perturbation of regulatory pathways. For example, transcriptional dysregulation of BER proteins in breast cancer has been studied by expression profiling.
DNA repair assays
Comet assays, alkaline unwinding, and BER-specific reporter assays measure repair capacity. These assays can be combined with CRISPR models to quantify the impact of regulatory genes on BER rate and extent.
Imaging and localization studies
Fluorescence microscopy of tagged BER proteins (e.g., GFP-APE1, GFP-XRCC1) allows real-time tracking of repair complex assembly at damage sites. This helps define how regulatory modifications affect recruitment.
How CRISPR Can Be Used to Study GO:1905051 regulation of base-excision repair
Knockout
CRISPR knockout of BER regulatory genes (e.g., OGG1, XRCC1, RBM39) is used to determine whether loss of the gene alters BER capacity, mutation load, or sensitivity to DNA-damaging agents. Knockout models are essential for causal inference.
Point Mutation
Point-mutation knock-in allows precise editing of post-translational modification sites, such as lysine residues targeted by ubiquitylation or acetylation, to test their role in regulating BER protein function.
Knock-in
Knock-in of disease-associated variants (e.g., MUTYH or NTHL1 mutations) into cell lines or organoids enables functional assessment of how these variants affect BER regulation and disease phenotypes.
Overexpression
Overexpression of BER regulatory genes, such as RBM39 or OGG1, is used to model gain-of-function effects in cancer progression and to test therapeutic targeting.
How EDITGENE Supports regulation of base-excision repair Research
Researchers studying regulation of base-excision repair-related genes often need to determine whether a candidate gene is causally involved in DNA repair, genome stability, or disease progression. EDITGENE provides a comprehensive suite of CRISPR-based services to generate precisely engineered cell models for such studies.
Contact EDITGENE today to design your custom CRISPR model for regulation of base-excision repair research.
Frequently Asked Questions About regulation of base-excision repair
What is GO:1905051?
GO:1905051 is the Gene Ontology term for regulation of base-excision repair, defined as any process that modulates the frequency, rate or extent of base-excision repair.
What genes are involved in regulation of base-excision repair?
Key genes include OGG1, APE1, XRCC1, PARP1, POLB, LIG3, SIRT1, SIRT6, and RBM39, among others.
How is base-excision repair regulated?
BER is regulated by post-translational modifications such as ubiquitylation and acetylation, NAD+-dependent signaling, and transcriptional/post-transcriptional control.
Why is regulation of base-excision repair important in cancer?
Dysregulation of BER regulation can lead to genomic instability and tumor progression, and it influences responses to DNA-damaging therapies.
What diseases are linked to defective regulation of base-excision repair?
Cancer, neurodegeneration, and metabolic/aging-related diseases have been linked to defective BER regulation.
What experimental models are used to study regulation of base-excision repair?
CRISPR knockout, point-mutation knock-in, overexpression cell lines, and CRISPR library screening are commonly used.
How does NAD+ regulate base-excision repair?
NAD+ serves as a substrate for PARP1 and sirtuins, which modulate BER activity in response to metabolic status.
What is the role of ubiquitylation in base-excision repair?
Ubiquitylation of BER proteins controls their stability, localization, and assembly into repair complexes.
What is the role of acetylation in base-excision repair?
Acetylation of BER proteins can alter their catalytic activity and interactions, fine-tuning repair capacity.
How can CRISPR help study regulation of base-excision repair?
CRISPR enables knockout, point-mutation knock-in, and overexpression of BER regulatory genes to test their causal roles in repair and disease.
Conclusion
GO:1905051, regulation of base-excision repair, is a critical biological process that controls the rate and extent of DNA base lesion removal. Its dysregulation is implicated in cancer, neurodegeneration, and metabolic disease. Understanding the molecular mechanisms, key genes, and regulatory layers of BER provides opportunities for therapeutic intervention and biomarker development. CRISPR-based models and screening approaches are powerful tools for dissecting this process and translating findings into clinical applications.
References
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- 2. Chatterjee N et al.. 2017. Mechanisms of DNA damage, repair, and mutagenesis.. Environ Mol Mutagen 58(5):235-263 PMID: 28485537
- 3. Edmonds MJ et al.. 2014. Regulation of base excision repair proteins by ubiquitylation.. Exp Cell Res 329(1):132-8 PMID: 25108137
- 4. Zhao S et al.. 2021. Significance of base excision repair to human health.. Int Rev Cell Mol Biol 364:163-193 PMID: 34507783
- 5. Bhakat KK et al.. 2020. Fine-tuning of DNA base excision/strand break repair via acetylation.. DNA Repair (Amst) 93:102931 PMID: 33087268
- 6. Wright G et al.. 2020. Transcriptional dysregulation of base excision repair proteins in breast cancer.. DNA Repair (Amst) 93:102922 PMID: 33087263
- 7. An H et al.. 2025. RBM39 Promotes Base Excision Repair to Facilitate the Progression of HCC by Stabilising OGG1 mRNA.. Cell Prolif 58(10):e70059 PMID: 40364450
- 8. Caldecott KW. 2022. DNA single-strand break repair and human genetic disease.. Trends Cell Biol 32(9):733-745 PMID: 35643889
