GO:0097698 telomere maintenance via base-excision repair: Mechanism, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0097698 describes a telomere maintenance process that uses base-excision repair (BER) to remove oxidative and other DNA damage from G-rich telomeric repeats.
• Telomeric DNA is unusually vulnerable to oxidative lesions because of its G-rich sequence, making BER a critical protective pathway at chromosome ends.
• Key BER enzymes implicated in telomere maintenance include APE1, FEN1, EXO1, DNA2, and CSB, which process abasic sites, flaps, and oxidative damage.
• Loss of BER capacity, such as reduced APE1 abundance, can cause failure of base-excision repair and telomere dysfunction in human cells.
• Interstitial telomeric sequences can promote gross chromosomal rearrangements, highlighting the importance of telomeric DNA stability.
• Experimental models for GO:0097698 include CRISPR knockout, point-mutation, knock-in, and overexpression cell lines targeting BER and telomere factors.
Description
GO:0097698, telomere maintenance via base-excision repair, is a biological process in which cells preserve telomeric DNA integrity by removing damaged bases through the base-excision repair (BER) pathway. Telomeres are G-rich repetitive sequences at chromosome ends, and this composition makes them particularly susceptible to oxidative DNA damage, including 8-oxoguanine and abasic sites. When such lesions are not repaired, they can interfere with telomere function and contribute to genome instability. This GO term therefore captures a specialized DNA repair function that operates specifically at telomeres to counteract endogenous and exogenous DNA damage. Researchers study GO:0097698 because telomere maintenance is central to cellular aging, cancer, and genome stability. BER proteins such as APE1, FEN1, EXO1, and DNA2 have been linked to the processing of damaged telomeric DNA and to broader DNA repair networks. Defects in BER factors can lead to telomere dysfunction and chromosomal rearrangements, underscoring the importance of this pathway for cell survival and disease prevention. Understanding how BER is coordinated at telomeres provides insight into how cells balance repair with telomere protection. This article summarizes the definition, mechanism, key genes, disease relevance, and experimental approaches for studying GO:0097698. It is intended for researchers who need a concise, citation-backed overview of telomere maintenance via base-excision repair and who may wish to model this process using CRISPR-based cell models.
telomere maintenance via base-excision repair At A Glance
| GO ID | GO:0097698 |
|---|---|
| GO term | telomere maintenance via base-excision repair |
| Ontology | biological_process |
| Synonym | None listed |
| Major function | Removal of damaged bases and abasic sites from telomeric DNA via base-excision repair to maintain telomere integrity |
| Key enzymes | APE1, FEN1, EXO1, DNA2, CSB |
| Substrate | Oxidatively damaged and abasic sites in G-rich telomeric DNA |
| Related process | Base-excision repair (BER) and telomere maintenance |
| Disease relevance | Genome instability, cancer, and stem cell dysfunction |
What Is GO:0097698?
GO:0097698 is defined as a telomere maintenance process that occurs by base-excision repair of telomeric DNA in response to DNA damage. Telomeric sequences are particularly susceptible to oxidative DNA damage due to their G-rich nature, and BER removes damaged bases and abasic sites to preserve telomere integrity.
Why Is telomere maintenance via base-excision repair Important in Cell Biology?
GO:0097698 is important because telomeres are essential for chromosome end protection, and their G-rich sequence makes them highly vulnerable to oxidative damage that must be repaired by BER. Failure of BER at telomeres can lead to persistent DNA lesions, telomere dysfunction, and chromosomal rearrangements, which are hallmarks of cancer and aging-related disorders. Studying this process helps explain how cells maintain genome stability and how BER defects contribute to human disease.
• Telomeric DNA is G-rich and therefore highly susceptible to oxidative damage, making BER essential for telomere integrity.
• APE1 processes abasic sites in telomeric i-motif DNA and cooperates with PCBP1 to maintain telomeric stability.
• FEN1 nuclease functions in DNA repair and is linked to cancer, highlighting its relevance to telomere maintenance.
• EXO1 is a tightly regulated nuclease involved in DNA repair and telomere processing.
• DNA2 (hDNA2) is a potential target for cancer and other diseases, reflecting its role in DNA repair and telomere maintenance.
• CSB protects genome integrity under oxidative stress, connecting BER-related factors to stress responses.
• Reduced APE1 abundance causes failure of base-excision repair in human embryonic stem cells, linking BER to stem cell biology.
• Interstitial telomeric sequences promote gross chromosomal rearrangement, emphasizing the need for telomere stability.
• Defects in BER at telomeres can contribute to cancer and degenerative diseases.
• Understanding GO:0097698 supports development of targeted therapies and CRISPR models for telomere-related disorders.
What Happens During telomere maintenance via base-excision repair?
Recognition of oxidative damage in telomeric DNA
In simple terms: The cell detects damaged bases in the G-rich telomere repeats.
Telomeric DNA is rich in guanine and is therefore prone to oxidative lesions such as 8-oxoguanine and abasic sites. BER is initiated when damage-specific glycosylases recognize and remove damaged bases, creating abasic sites that must be further processed. This step is critical because unrepaired lesions can block telomere function and lead to genome instability.
Cleavage of abasic sites by APE1
In simple terms: APE1 cuts the DNA backbone at the damaged site to prepare it for repair.
APE1 binds and processes abasic sites present in telomeric i-motif DNA and cooperates with PCBP1 in maintenance of telomeric stability. APE1 incises the abasic site, generating a single-strand break with a 5'-deoxyribose phosphate terminus that is further processed by downstream BER enzymes. This activity is essential for completing BER at telomeres and preventing accumulation of repair intermediates.
Flap processing and gap filling by FEN1 and DNA2
In simple terms: Specialized enzymes trim and seal the DNA after the damaged base is removed.
FEN1 is a nuclease that functions in DNA repair and has been linked to cancer, and it is involved in processing flap structures that arise during BER. DNA2 (hDNA2) is another nuclease implicated in DNA repair and telomere maintenance, and it is considered a potential target for cancer and other diseases. Together, these enzymes help complete repair synthesis and ligation at telomeric sites.
Coordination with EXO1 and CSB under oxidative stress
In simple terms: Other repair factors help regulate and support the BER process at telomeres.
EXO1 is a tightly regulated nuclease that participates in DNA repair and telomere processing. CSB protein plays a protective role in maintaining genome integrity in human cells under oxidative stress, linking BER-related factors to stress responses. These proteins help coordinate BER with other DNA repair pathways to ensure telomere stability.
Consequences of BER failure at telomeres
In simple terms: If BER does not work, telomeres become unstable and chromosomes can rearrange.
Decrease in abundance of apurinic/apyrimidinic endonuclease causes failure of base excision repair in culture-adapted human embryonic stem cells, demonstrating that BER capacity is required for genome maintenance. Interstitial telomeric sequences promote gross chromosomal rearrangement via multiple mechanisms, showing that telomeric DNA instability can drive large-scale genome changes. Thus, defective BER at telomeres can lead to chromosomal rearrangements and cellular dysfunction.
Key Genes Involved in GO:0097698 telomere maintenance via base-excision repair
The following genes and proteins are experimentally implicated in telomere maintenance via base-excision repair or in related BER and telomere stability processes.
| Gene | Major Role | Research Relevance |
|---|---|---|
| APE1 | Processes abasic sites in telomeric i-motif DNA and cooperates with PCBP1 | Key BER enzyme for telomere stability; target for oxidative damage studies |
| PCBP1 | Cooperates with APE1 in maintenance of telomeric stability | RNA-binding protein with roles in telomere maintenance |
| FEN1 | Nuclease involved in DNA repair and flap processing | Linked to cancer; important for BER completion |
| EXO1 | Tightly regulated nuclease in DNA repair and telomere processing | Regulates resection and repair at telomeres |
| DNA2 | Nuclease/helicase involved in DNA repair and telomere maintenance | Potential target for cancer and other diseases |
| CSB | Protects genome integrity under oxidative stress | Links BER-related stress responses to genome stability |
| TFIIH | Transcription/DNA repair factor with emerging functions | Connects transcription and repair pathways |
| OGG1 | Initiates BER by removing oxidized guanine (general BER factor) | Relevant to oxidative damage in G-rich telomeres |
| XRCC1 | Scaffold protein in BER (general BER factor) | Supports BER complex assembly |
| LIG3 | DNA ligase in BER (general BER factor) | Seals repair intermediates |
| PARP1 | Poly(ADP-ribose) polymerase in DNA repair (general BER factor) | Sensors DNA breaks and recruits repair factors |
| PCNA | Processivity factor for DNA polymerases in repair (general BER factor) | Supports repair synthesis |
| POLB | DNA polymerase in BER (general BER factor) | Fills gaps during BER |
| TERF1 | Telomere shelterin component (general telomere factor) | Protects telomeres and coordinates repair |
| TERF2 | Telomere shelterin component (general telomere factor) | Prevents inappropriate repair at telomeres |
| POT1 | Shelterin component binding single-stranded telomeric DNA (general telomere factor) | Regulates telomere overhang processing |
| TPP1 | Shelterin component interacting with POT1 (general telomere factor) | Recruits telomerase and protects telomeres |
| RAP1 | Shelterin component (general telomere factor) | Regulates telomere length and repair |
How Is telomere maintenance via base-excision repair Regulated?
The process of telomere maintenance via base-excision repair is regulated by the availability and activity of BER enzymes such as APE1, FEN1, EXO1, and DNA2. APE1 abundance is critical, as decreased APE1 causes failure of base excision repair in human embryonic stem cells. EXO1 is a tightly regulated nuclease, indicating that its activity is controlled to prevent inappropriate resection. CSB protects genome integrity under oxidative stress, suggesting that stress-responsive factors modulate BER at telomeres. Additionally, shelterin components and PCBP1 cooperate with BER enzymes to maintain telomeric stability.
telomere maintenance via base-excision repair and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| APE1 | Stem cell dysfunction, genome instability | APE1 knockout or knockdown in human embryonic stem cells |
| FEN1 | Cancer, DNA repair deficiency | FEN1 knockout cancer cell lines |
| DNA2 | Cancer and other diseases | DNA2 knockout or overexpression models |
| EXO1 | DNA repair disorders, cancer predisposition | EXO1 point-mutation knock-in cell lines |
| CSB | Oxidative stress sensitivity, genome instability | CSB knockout cells under oxidative stress |
Cancer and genome instability
Defects in BER at telomeres can lead to chromosomal rearrangements and genome instability, which are hallmarks of cancer. FEN1 and DNA2 are linked to cancer, and their roles in DNA repair and telomere maintenance make them potential therapeutic targets. Interstitial telomeric sequences promote gross chromosomal rearrangement, further connecting telomere instability to cancer-associated genome changes.
Stem cell dysfunction and aging
Reduced APE1 abundance causes failure of base excision repair in culture-adapted human embryonic stem cells, indicating that BER is required for stem cell genome maintenance. Telomere dysfunction is associated with aging-related phenotypes, and oxidative damage to G-rich telomeres may contribute to cellular senescence. Thus, GO:0097698 is relevant to stem cell biology and aging research.
Oxidative stress-related disorders
CSB protects genome integrity under oxidative stress, linking BER-related factors to cellular stress responses. Telomeric DNA is particularly susceptible to oxidative damage, and failure to repair such lesions can contribute to degenerative processes. Understanding how BER operates at telomeres may inform research on oxidative stress-related diseases.
From telomere maintenance via base-excision repair-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does loss of APE1 impair BER at telomeres? | APE1 knockout cell line |
| Does FEN1 mutation affect telomere stability? | FEN1 point-mutation knock-in |
| How does DNA2 overexpression affect telomere maintenance? | DNA2 overexpression cell model |
| Does EXO1 regulation impact telomeric resection? | EXO1 tagged knock-in for live imaging |
| Does CSB protect telomeres under oxidative stress? | CSB knockout under oxidative stress |
| Can PCBP1 cooperate with APE1 at telomeres? | PCBP1 knockout or tagged knock-in |
How to Study the telomere maintenance via base-excision repair Process
| Method | What It Measures | Typical Application |
|---|---|---|
| CRISPR knockout screen | Gene requirement for telomere maintenance | Identify BER genes affecting telomere stability |
| Point-mutation knock-in | Effect of specific mutations on BER activity | Study catalytic residues in FEN1 or EXO1 |
| Tagged knock-in | Protein localization at telomeres | Track APE1 or PCBP1 at telomeres |
| Telomere length assay | Telomere length changes | Assess telomere maintenance defects |
| Chromosomal rearrangement assay | Gross chromosomal rearrangements | Detect genome instability from telomere dysfunction |
| Oxidative stress assay | Cell survival under oxidative stress | Test CSB or APE1 protective roles |
| BER activity assay | Base excision repair capacity | Measure repair of abasic sites in telomeric DNA |
| Proteomics | Protein interactions in BER complexes | Identify APE1 and PCBP1 partners |
CRISPR knockout screens
CRISPR knockout screens can identify genes required for telomere maintenance via BER by disrupting candidate BER factors and measuring telomere dysfunction or cell survival. For example, APE1 knockout causes failure of base excision repair in human embryonic stem cells. Such screens help systematically map the genetic network of GO:0097698.
Point-mutation and knock-in models
Point mutations in BER enzymes such as FEN1 or EXO1 can be introduced to study catalytic residues or regulatory sites. Knock-in of tagged versions of APE1 or PCBP1 allows tracking of protein localization at telomeres. These models provide mechanistic insight into how specific residues contribute to telomere maintenance.
Telomere dysfunction assays
Telomere dysfunction can be assessed by measuring telomere length, telomere-induced foci, and chromosomal rearrangements. Interstitial telomeric sequences promote gross chromosomal rearrangement, which can be detected by cytogenetic methods. These assays are used to evaluate the impact of BER gene perturbations on telomere stability.
Oxidative stress and BER activity assays
Oxidative stress treatments combined with BER activity assays can measure the capacity of cells to repair damaged telomeric DNA. CSB protects genome integrity under oxidative stress, and its loss can sensitize cells to oxidative damage. APE1 activity can be measured using abasic site-containing substrates.
How CRISPR Can Be Used to Study GO:0097698 telomere maintenance via base-excision repair
Knockout
CRISPR knockout of BER genes such as APE1, FEN1, DNA2, or EXO1 can reveal their requirement for telomere maintenance via base-excision repair. For example, APE1 knockout causes failure of base excision repair in human embryonic stem cells. Knockout models are useful for assessing telomere dysfunction and genome instability.
Point Mutation
Point mutations can be introduced into catalytic or regulatory residues of BER enzymes to dissect their functions in telomere maintenance. For instance, mutations in FEN1 nuclease domains can affect flap processing and cancer-related phenotypes. EXO1 regulation can be studied by mutating phosphorylation or interaction sites.
Knock-in
Knock-in of tagged or reporter versions of APE1, PCBP1, or other BER factors allows visualization and biochemical isolation of repair complexes at telomeres. Tagged knock-in models can also be used to study protein dynamics under oxidative stress. These models help define how BER proteins are recruited to telomeric DNA.
Overexpression
Overexpression of DNA2 or other BER factors can test whether increased repair activity protects telomeres or alters telomere length. Overexpression models are useful for studying gain-of-function effects in cancer and aging. They can also be combined with oxidative stress to assess protective roles.
How EDITGENE Supports telomere maintenance via base-excision repair Research
Researchers studying telomere maintenance via base-excision repair-related genes often need to determine whether a candidate gene is causally involved in telomere stability, DNA repair, or disease-associated phenotypes. EDITGENE provides CRISPR-based cell model services to enable such functional studies with precision and reproducibility.
Contact EDITGENE today to design your custom CRISPR model for telomere maintenance via base-excision repair research.
Frequently Asked Questions About telomere maintenance via base-excision repair
What is GO:0097698?
GO:0097698 is the Gene Ontology term for telomere maintenance via base-excision repair, a process that removes DNA damage from telomeric DNA using BER.
What genes are involved in telomere maintenance via base-excision repair?
Key genes include APE1, PCBP1, FEN1, EXO1, DNA2, and CSB, which process abasic sites, flaps, and oxidative damage at telomeres.
Why are telomeres susceptible to oxidative damage?
Telomeric DNA is G-rich, making it particularly susceptible to oxidative DNA damage such as 8-oxoguanine and abasic sites.
How does APE1 function in telomere maintenance?
APE1 binds and processes abasic sites in telomeric i-motif DNA and cooperates with PCBP1 to maintain telomeric stability.
What happens when base-excision repair fails at telomeres?
Failure of BER can lead to telomere dysfunction, chromosomal rearrangements, and genome instability.
Is telomere maintenance via base-excision repair linked to cancer?
Yes, defects in BER at telomeres can cause genome instability, and FEN1 and DNA2 are linked to cancer.
What experimental models are used to study GO:0097698?
CRISPR knockout, point-mutation, knock-in, and overexpression cell models targeting BER genes are commonly used.
How can CRISPR screens help study telomere maintenance via BER?
CRISPR knockout screens can identify genes required for telomere stability and BER, such as APE1 and FEN1.
What is the role of CSB in telomere maintenance?
CSB protects genome integrity in human cells under oxidative stress, linking it to BER-related stress responses.
Can EDITGENE provide custom cell models for GO:0097698 research?
Yes, EDITGENE offers knockout, point-mutation, knock-in, overexpression, library screening, and bioinformatics services for telomere maintenance via base-excision repair research.
Conclusion
GO:0097698, telomere maintenance via base-excision repair, is a specialized DNA repair process that protects G-rich telomeric DNA from oxidative damage. Key enzymes such as APE1, FEN1, EXO1, DNA2, and CSB coordinate to remove lesions and preserve telomere integrity, and their dysfunction is linked to genome instability, cancer, and stem cell defects. Studying this process with CRISPR-based models can reveal causal mechanisms and support development of targeted therapies.
References
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- 3. Low GKM et al.. 2025. Protective role of Cockayne Syndrome B (CSB) protein in maintaining genome integrity in human cells under oxidative stress.. Mutat Res Genet Toxicol Environ Mutagen 907:503887 PMID: 41167909
- 4. Jia PP et al.. 2017. Role of human DNA2 (hDNA2) as a potential target for cancer and other diseases: A systematic review.. DNA Repair (Amst) 59:9-19 PMID: 28903076
- 5. Zheng L et al.. 2011. Functional regulation of FEN1 nuclease and its link to cancer.. Nucleic Acids Res 39(3):781-94 PMID: 20929870
- 6. Bellina A et al.. 2026. APE1 binds and processes abasic sites present in i-motif DNA and cooperates with PCBP1 in maintenance of telomeric stability.. Nucleic Acids Res 54(13) PMID: 42417194
- 7. Rosas Bringas FR et al.. 2024. Interstitial telomeric sequences promote gross chromosomal rearrangement via multiple mechanisms.. Proc Natl Acad Sci U S A 121(49):e2407314121 PMID: 39602274
- 8. Krutá M et al.. 2013. Decrease in abundance of apurinic/apyrimidinic endonuclease causes failure of base excision repair in culture-adapted human embryonic stem cells.. Stem Cells 31(4):693-702 PMID: 23315699
