WRN Antibodies

Background

WRN gene encoding a belongs to the RecQ helicase family nucleoprotein, mainly involved in DNA repair, critical cellular processes such as replication and transcription regulation. The protein produced by this gene has helicase and exonuclease activities, which can maintain genomic stability and prevent abnormal recombination. Research has found that mutations in the WRN gene can lead to Werner's syndrome, a genetic disorder characterized by premature aging, in which patients exhibit accelerated aging and multi-system dysfunction. In 1996, scientists first identified the WRN gene, which is unique in that it simultaneously possesses the dual functions of a helicase and an exonuctase. As an important aging-related gene, WRN has become an important model for studying DNA damage repair and the mechanisms of aging, providing key clues for understanding biological processes such as cellular aging and cancer occurrence.

Structure Function Application Advantage Our Products

Structure of WRN

The WRN gene encodes a RecQ helicase (with a molecular weight of approximately 162 kDa), which plays a crucial role in DNA repair, replication, and maintaining genomic stability. The molecular weight of this protein is relatively conserved among different species, but there may be minor differences.

Species	Human	Mouse	Rat
Molecular Weight (kDa)	~161	~162	~161
Primary Structural Differences	Contains helicase and exonuclease domains	Highly homologous and functionally similar	Highly similar to the human WRN protein

The WRN protein is composed of 1432 amino acids and has a typical DEXH-box and exonuclide domain, enabling it to unwind DNA double strands and degrade erroneous strands. Its tertiary structure forms a functional complex and relies on ATP hydrolysis to provide energy. Mutations in the WRN protein can lead to Werner syndrome, which is characterized by premature aging and genomic instability.

Fig. 1:Targeted proteasomal degradation of trapped WRN upon treatment with WRNi. Fig. 1 Proposed model for targeted proteasomal degradation of trapped WRN upon treatment with WRNi.¹

Key structural properties of WRN:

RecQ helicase domain
Exonuclease domain
RQC (RecQ C-terminal) domain
HRDC (Helicase and RNaseD C-terminal) domain
Verified location Signal (NLS)

Functions of WRN

The protein encoded by the WRN gene is a multifunctional DNA helicase that plays a core role in maintaining genomic stability. Its main functions include:

Function	Description
DNA repair	Participate in homologous recombination repair (HR), non-homologous end join (NHEJ), and base excision repair (BER) to ensure the correct repair of DNA damage.
DNA replication	During the DNA replication process, complex secondary structures (such as G-tetrasons) are untangled to prevent replication fork arrest and genomic breaks.
Telomere maintenance	Synergistic action with telomerase to prevent abnormal telomere shortening and delay cell aging.
Transcriptional regulation	Regulate the transcription of specific genes and affect cell cycle and apoptosis-related pathways.
Genomic stability	Prevent the recombination and accumulation of chromosomal abnormalities and mutations, and reduce the risk of cancer.

Functional defects of the WRN protein can lead to Werner syndrome, which is characterized by premature aging, genomic instability and cancer susceptibility. In addition, WRN has potential target value in cancer treatment, especially in tumors that rely on DNA damage repair mechanisms.

Applications of WRN and WRN Antibody in Literature

1. Datta, Arindam, et al. "WRN helicase safeguards deprotected replication forks in BRCA2-mutated cancer cells." Nature communications 12.1 (2021): 6561. https://doi.org/10.1038/s41467-021-26811-w

Studies have shown that in BRCA2-deficient cancer cells, WRN helicase maintains genomic stability by repairing the stalled replication fork and inhibiting the activity of MRE11 nuclease. Inhibition of WRN can trigger MRE11-mediated fork degradation, leading to DNA breaks and chromosomal abnormalities, enhancing the sensitivity of BRCA2-deficient cells to PARP inhibitors and inhibiting tumor growth.

2. Orren, David K., and Amrita Machwe. "Response to replication stress and maintenance of genome stability by WRN, the Werner syndrome protein." International Journal of Molecular Sciences 25.15 (2024): 8300. https://doi.org/10.3390/ijms25158300

Studies have shown that defects in the WRN gene lead to Werner syndrome (WS), which is characterized by premature aging and genomic instability. The WRN protein has functions such as helicase and exonuclease, and is involved in replication stress response and telomere maintenance, but its exact mechanism is not yet fully understood. The WS study provides important clues for the association between aging and DNA damage.

3. Morales-Juarez, David A., and Stephen P. Jackson. "Clinical prospects of WRN inhibition as a treatment for MSI tumours." NPJ Precision Oncology 6.1 (2022): 85. https://doi.org/10.1038/s41698-022-00319-y

The article indicates that WRN helicase has a synthetic lethal effect on microsatellite instability (MSI) tumors. Inhibiting WRN is expected to become a new targeted therapy strategy, but its clinical application still faces challenges, and further optimization of inhibitor development and indication screening is needed.

4. Rodríguez Pérez, Fernando, et al. "WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis." Nature Communications 15.1 (2024): 6059. https://doi.org/10.1038/s41467-024-50178-3

The research discovered the dynamic regulatory mechanism of WRN helicase in MSI-H cancer cells: The inhibitor mediates its degradation through p97/VCP, and the PIAS4-RNF4 axis regulates this process. Combined inhibition of WRN and SUMOylation can enhance the cytotoxicity of MSI-H cells, providing a new strategy for targeted therapy.

5. Cortes-Cros, Marta, et al. "Discovery of WRN inhibitor HRO761 with synthetic lethality in MSI cancers." Nature (2024). https://doi.org/10.1038/s41586-024-07350-y

Research has found that in the clinical stage, the WRN helicase inhibitor HRO761 locks the inactivation of WRN by allosteric binding to the D1-D2 interface, selectively inducing DNA damage and growth inhibition in MSI tumor cells, and its efficacy has been verified in the PDX model. Currently, relevant clinical trials are underway.

Creative Biolabs: WRN Antibodies for Research

Creative Biolabs specializes in the production of high-quality WRN antibodies for research and industrial applications. Our portfolio includes monoclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom WRN Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our WRN antibodies, custom preparations, or technical support, contact us at email.

Reference

Rodríguez Pérez, Fernando, et al. "WRN inhibition leads to its chromatin-associated degradation via the PIAS4-RNF4-p97/VCP axis." Nature Communications 15.1 (2024): 6059. https://doi.org/10.1038/s41467-024-50178-3