ERCC4 (Excision Repair Cross-Complementing 4), also known as XPF, is a structure-specific endonuclease that forms a complex with ERCC1 to participate in multiple DNA repair pathways. This protein plays critical roles in nucleotide excision repair (NER) and interstrand crosslink (ICL) repair mechanisms . ERCC4's biological significance is underscored by the fact that mutations in this gene can lead to three distinct clinical disorders depending on the mutation type: Fanconi anemia (FA-Q subtype), xeroderma pigmentosum (XP-F), or XFE progeroid syndrome . The ERCC4-ERCC1 complex functions as a 5' endonuclease that makes incisions during DNA repair processes, acting downstream of FANCD2 monoubiquitination in the Fanconi anemia pathway .
ERCC4 antibodies have been validated across multiple experimental applications with specific dilution recommendations:
When using these antibodies, researchers should optimize conditions for their specific experimental systems, as antibody performance can be sample-dependent .
Biotin-conjugated ERCC4 antibodies offer several methodological advantages:
Enhanced signal amplification: The biotin-streptavidin system provides one of the strongest non-covalent interactions in biology (Kd ≈ 10^-15 M), allowing for superior signal amplification in detection systems.
Versatile detection options: Compatible with various streptavidin-conjugated reporter molecules (fluorophores, enzymes, quantum dots), enabling flexible experimental design.
Multi-labeling capability: Facilitates simultaneous detection of multiple targets in co-localization studies, particularly valuable when examining ERCC4 interactions with other DNA repair proteins.
Reduced background in certain tissues: The biotin-streptavidin system can provide cleaner results in tissues with high endogenous immunoglobulin levels.
Stability advantage: Biotin conjugation can increase antibody shelf-life and resistance to denaturation during experimental procedures.
When using biotin-conjugated antibodies, researchers should block endogenous biotin (particularly in tissues like liver, kidney, and brain) using streptavidin/avidin blocking kits to minimize background signal.
Optimal conditions for ERCC4 detection vary by application:
For Immunohistochemistry:
Antigen retrieval: TE buffer (pH 9.0) is recommended; citrate buffer (pH 6.0) can be used as an alternative
Fixation: 10% neutral buffered formalin for FFPE tissues
For Immunofluorescence:
Fixation: 4% paraformaldehyde (10-15 minutes) for cultured cells
Permeabilization: 0.1-0.5% Triton X-100 (5-10 minutes) for nuclear protein access
For Western Blotting:
Lysis buffers containing protease inhibitors are essential
Sample heating at 95°C for 5 minutes in reducing sample buffer
Expected molecular weight: Approximately 104 kDa (calculated), though observed at ~38 kDa in some systems
Since ERCC4 is primarily nuclear and associates with chromatin during DNA repair, nuclear extraction protocols may yield better results for certain applications.
A robust experimental design requires these controls:
Positive Controls:
Negative Controls:
ERCC4 knockdown/knockout cell lines
Isotype control (matched IgG class with no specific target)
Secondary antibody-only control
Specificity Controls:
Pre-absorption with immunizing peptide/protein
For biotin-conjugated antibodies: streptavidin-only control to assess endogenous biotin
These controls help distinguish specific signal from background and validate antibody specificity, particularly important when studying proteins involved in complex repair pathways.
ERCC4 antibodies provide powerful tools for investigating mutation consequences through multiple methodological approaches:
Protein Expression Analysis: Western blotting can reveal if mutations affect protein stability or expression levels. Research has shown that certain mutations like p.Arg689Ser maintain protein expression while others lead to truncated or unstable protein products .
Subcellular Localization Studies: Immunofluorescence can determine if mutations alter nuclear localization or chromatin association. Studies have demonstrated that some XP-F causing mutations result in cytoplasmic aggregation, while FA-causing mutations maintain nuclear localization .
Functional Complementation Assays: Using ERCC4 antibodies to monitor protein expression in genetic complementation studies where wild-type or mutant ERCC4 is introduced into deficient cells. This approach has been used to confirm that p.Leu230Pro and p.Arg689Ser mutations fail to complement MMC sensitivity in ERCC4-null cells .
Protein-Protein Interaction Analysis: Co-immunoprecipitation studies can assess if mutations disrupt the ERCC4-ERCC1 complex formation, essential for nuclease activity .
DNA Damage Response Pathway Analysis: Combined with markers of DNA damage (γH2AX) or repair intermediates (RAD51 foci), ERCC4 antibodies can help determine how mutations affect response to specific DNA damaging agents .
This multi-faceted approach has revealed that FA-causing ERCC4 mutations specifically compromise ICL repair without severely affecting nucleotide excision repair, explaining the distinct clinical presentation .
When facing contradictory results with ERCC4 antibodies, researchers should consider these methodological approaches:
Antibody Validation Hierarchy:
Genetic approach: Test in ERCC4 knockout/knockdown systems
Biochemical approach: Immunoprecipitation followed by mass spectrometry
Independent antibody approach: Use multiple antibodies targeting different epitopes
Epitope Accessibility Analysis:
ERCC4 undergoes conformational changes when bound to DNA or ERCC1
Some epitopes may be masked in certain protein complexes
Consider native versus denatured conditions in your experimental system
Cell-Type Specific Considerations:
ERCC4 expression levels vary across tissues and cell lines
Post-translational modifications may differ between cell types
DNA damage status affects ERCC4 localization and complex formation
Technical Optimization Matrix:
| Parameter | Variables to Test | Measurement Method |
|---|---|---|
| Antibody concentration | Serial dilutions | Signal-to-noise ratio |
| Blocking reagents | BSA vs. serum vs. commercial blockers | Background reduction |
| Incubation conditions | Time, temperature, buffer composition | Signal intensity and specificity |
| Detection systems | Direct vs. indirect, enzyme vs. fluorophore | Sensitivity and resolution |
Quantitative Validation Metrics:
Establish minimum acceptable specificity ratios
Implement statistical analysis of reproducibility
Consider absolute quantification using recombinant protein standards
By systematically addressing these factors, researchers can resolve contradictory results and establish reliable ERCC4 detection protocols.
Chromatin immunoprecipitation sequencing (ChIP-seq) with biotin-conjugated ERCC4 antibodies requires specific optimization:
DNA Damage Induction Protocols:
ERCC4 binding to chromatin is enhanced following DNA damage
Consider treatment with cisplatin (interstrand crosslinks) or UV (for NER substrates)
Time course experiments to capture transient interactions
Crosslinking Optimization:
Standard formaldehyde (1%) may be insufficient for transient interactions
Test dual crosslinkers (formaldehyde plus disuccinimidyl glutarate)
Crosslinking time should be optimized (5-15 minutes) to prevent over-crosslinking
Sonication Parameters:
Target fragment size: 200-300bp for high-resolution binding site identification
Verify fragmentation efficiency by agarose gel electrophoresis
Consider enzymatic fragmentation alternatives for specific chromatin environments
Biotin-Streptavidin Capture Strategy:
Pre-clear lysates with streptavidin beads to reduce background
Block endogenous biotin with free avidin before adding antibody
Consider sequential ChIP for interacting protein complexes (e.g., ERCC4-ERCC1)
Bioinformatic Analysis Considerations:
Use appropriate peak calling algorithms sensitive to repair protein binding patterns
Compare damage-induced versus constitutive binding sites
Integrate with DNA damage mapping data (e.g., XR-seq) for functional correlation
This approach has successfully identified ERCC4 binding at sites of DNA damage and revealed unexpected roles in regulating gene expression at promoter regions.
Multiplexed detection of ERCC4 alongside other DNA repair proteins requires careful experimental design:
Antibody Selection Criteria:
Choose antibodies raised in different host species
Verify no cross-reactivity between detection systems
Ensure compatible fixation/permeabilization requirements
Biotin-Conjugated ERCC4 Advantage:
The biotin-streptavidin system provides flexible detection options
Can be visualized last in sequential staining protocols
Compatible with tyramide signal amplification for low-abundance detection
Recommended Multiplex Panel for DNA Repair Studies:
| Protein | Function | Recommended Labeling | Subcellular Localization |
|---|---|---|---|
| ERCC4 (XPF) | Endonuclease | Biotin-conjugated + streptavidin-fluorophore | Nuclear |
| ERCC1 | ERCC4 binding partner | Direct fluorophore conjugate | Nuclear |
| FANCD2 | FA pathway marker | Direct fluorophore conjugate | Nuclear foci |
| γH2AX | DNA damage marker | Direct fluorophore conjugate | Nuclear foci |
| RAD51 | Homologous recombination | Direct fluorophore conjugate | Nuclear foci |
Sequential Staining Protocol:
Start with lowest abundance target first
Include stringent washing steps between antibodies
Consider antibody stripping for highly multiplexed panels
Validate each antibody individually before combining
Advanced Imaging Considerations:
Spectral unmixing for overlapping fluorophores
Super-resolution techniques for co-localization studies
Live-cell compatible tags for real-time dynamics
This approach has successfully demonstrated the sequential recruitment of repair factors and temporal dynamics of ERCC4 function in response to DNA damage.
ERCC4 antibodies can differentiate pathway-specific functions through these methodological approaches:
Disease-Specific Model Systems:
Fanconi anemia patient-derived cells: Study ICL repair function
XP-F patient-derived cells: Focus on NER function
Cancer cell lines with altered ERCC4: Examine chemoresistance mechanisms
Pathway-Specific DNA Damage Induction:
Functional Separation Methods:
Chromatin fractionation to isolate DNA-bound ERCC4
Immunoprecipitation with pathway-specific partners
CRISPR-induced mutations affecting specific domains
Quantitative Analysis Approaches:
Microscopy-based repair kinetics measurements
Repair capacity correlation with ERCC4 expression levels
Structure-function analysis using domain-specific antibodies
Therapeutic Response Applications:
Monitor ERCC4 as a biomarker for chemotherapy response
Target pathway-specific functions for synthetic lethality
Evaluate ERCC4 status in personalized medicine approaches
Studies have demonstrated that specific ERCC4 mutations like p.Arg689Ser disrupt ICL repair while preserving NER activity, explaining the Fanconi anemia phenotype without the photosensitivity typical of XP . This type of pathway-specific dysfunction analysis has significant implications for understanding disease mechanisms and developing targeted therapies.
Western blot detection of ERCC4 requires attention to several technical factors:
Sample Preparation Considerations:
Nuclear extraction protocols improve detection of chromatin-bound ERCC4
Gentle lysis conditions help preserve protein-protein interactions
Protease inhibitors are essential to prevent degradation
Protein Size and Detection Parameters:
Gel/Transfer Optimization:
8% SDS-PAGE gels provide optimal resolution in the 100 kDa range
Extended transfer times (overnight at low voltage) improve high-molecular-weight protein transfer
PVDF membranes offer better protein retention than nitrocellulose for large proteins
Antibody Dilution Optimization:
Signal Development Strategies:
Enhanced chemiluminescence (ECL) provides good sensitivity
For low abundance detection, consider fluorescent detection systems
Quantitative analysis requires linear range determination
For reproducible results, standardize protein loading (25-50 μg per lane) and include appropriate positive controls like HeLa or MCF-7 cells .
Immunofluorescence protocols for ERCC4 require optimization based on experimental context:
Fixation Method Selection:
Paraformaldehyde (4%) preserves structural integrity
Methanol fixation can improve nuclear protein accessibility
Avoid glutaraldehyde which increases autofluorescence
Nuclear Antigen Accessibility:
Triton X-100 (0.1-0.5%) permeabilization is essential
Consider additional permeabilization with 0.5% saponin for dense chromatin
Pre-extraction with CSK buffer can reveal chromatin-bound fraction
Signal Enhancement Strategies:
For biotin-conjugated antibodies: Fluorescent streptavidin conjugates provide flexibility
Tyramide signal amplification can detect low abundance ERCC4
Anti-fading mounting media essential for quantitative imaging
Damage-Induced Foci Visualization:
Pre-treatment with DNA damaging agents (UV, MMC, cisplatin) induces foci formation
Time course experiments (0.5-24 hours post-damage) capture dynamic responses
Co-staining with γH2AX confirms DNA damage localization
Dilution Optimization by Context:
| Experimental Context | Suggested Dilution Range | Special Considerations |
|---|---|---|
| Cultured cell lines | 1:100-1:200 | Pre-extraction may help visualize chromatin-bound fraction |
| Primary cells | 1:50-1:100 | Lower antibody concentration reduces background |
| Tissue sections | 1:20-1:50 | Requires stringent antigen retrieval |
| DNA damage-induced | 1:100-1:200 | Optimize timepoint for maximum foci visualization |
Successful immunofluorescence has shown that ERCC4 forms discrete nuclear foci that co-localize with other repair factors following DNA damage .
Tissue-specific detection of ERCC4 presents unique challenges requiring specialized approaches:
Tissue-Specific Fixation Optimization:
Brain tissue: Shorter fixation times (6-12 hours) prevent overfixation
Skin samples: Required for XP studies, needs minimal fixation (4-6 hours)
Bone marrow: Critical for FA studies, requires specialized fixatives
Antigen Retrieval Requirements:
Endogenous Biotin Blocking:
Critical for biotin-conjugated antibodies
Particularly important in biotin-rich tissues (liver, kidney, brain)
Implement avidin/biotin blocking kit before antibody incubation
Background Reduction Strategies:
| Tissue Type | Common Challenge | Recommended Solution |
|---|---|---|
| Skin | High keratin background | Extended blocking (2+ hours), 0.1% Tween-20 in wash buffers |
| Bone marrow | Blood cell autofluorescence | Sudan Black B treatment (0.1-0.3%) |
| Brain | Lipofuscin autofluorescence | 0.1% Sudan Black B or TrueBlack® treatment |
| Liver | Endogenous biotin | Avidin-biotin blocking system, consider alternative conjugation |
Signal Amplification Options:
Tyramide signal amplification for low abundance detection
Multi-layer detection systems (biotin-streptavidin-tertiary enhancement)
Quantum dots for multiplexed detection with improved signal-to-noise ratio
These approaches have successfully detected ERCC4 in human tissues including testis, brain, ovary, skin, and spleen , enabling studies of pathway-specific functions in disease-relevant tissues.
Flow cytometry with biotin-conjugated ERCC4 antibodies requires specific optimization steps:
Cell Preparation Protocol:
Fixation: 2-4% paraformaldehyde (10-15 minutes)
Permeabilization: 90% ice-cold methanol or 0.1% Triton X-100
Critical: Gentle cell handling to maintain nuclear integrity
Antibody Titration Strategy:
Detection System Options:
Streptavidin-fluorophore conjugates (PE, APC, FITC)
Consider bright fluorophores (PE, PE-Cy7) for low-abundance targets
Tandem dyes provide flexible panel design options
Controls for Biotin-Based Systems:
Data Analysis Considerations:
Gating strategy: Exclude debris, select single cells, then viable cells
Compare mean fluorescence intensity (MFI) rather than percent positive
For inducible systems: Calculate fold change in MFI after DNA damage
This approach has successfully detected ERCC4 expression in transfected HEK293T cells and can be adapted to study endogenous expression in various cell types and experimental conditions.
Immunoprecipitation (IP) experiments with ERCC4 antibodies require careful design:
Elution and Detection Strategies:
For biotin-conjugated antibodies: Biotin competition elution preserves protein integrity
Standard elution: Gentle (native) or denaturing conditions depending on downstream applications
Western blot detection: Use clean detection systems to avoid antibody cross-reactivity
This approach has been successfully used to detect ERCC4 interaction partners in MCF-7 cells and can reveal damage-specific protein complexes when combined with appropriate DNA damaging agents.
ERCC4 antibodies can play crucial roles in personalizing cancer treatments:
Biomarker Development Applications:
Expression level analysis in tumor biopsies
Localization patterns as predictive indicators
Post-translational modification status assessment
Chemotherapy Response Prediction:
ERCC4 levels correlate with cisplatin resistance in multiple cancer types
Functional assays measuring repair capacity can guide therapy selection
Monitoring dynamic changes during treatment can predict acquired resistance
Synthetic Lethality Approaches:
Identify tumors with specific ERCC4 pathway defects
Match with complementary targeted therapies
Monitor pathway status during treatment
Methodological Integration in Clinical Workflows:
| Application | Methodology | Clinical Utility |
|---|---|---|
| Expression screening | IHC on tissue microarrays | Patient stratification |
| Functional assessment | Repair capacity assays in patient-derived models | Therapy selection |
| Mutation impact | Antibodies specific to common variants | Personalized dosing |
| Treatment monitoring | Serial liquid biopsies with ERCC4 detection | Resistance prediction |
Companion Diagnostic Development:
Standardized ERCC4 detection assays
Threshold determination for clinical decision-making
Validation in prospective clinical trials
These approaches leverage our understanding that FA-causing ERCC4 mutations specifically compromise ICL repair functions , potentially creating exploitable vulnerabilities in tumors with similar pathway alterations.
Advanced methodologies for studying ERCC4 in chromatin contexts include:
Proximity Ligation Assays (PLA):
Visualize ERCC4 interactions with specific partners in situ
Detect transient repair complexes at damage sites
Quantify interaction dynamics during repair progression
Chromatin Immunoprecipitation Innovations:
CUT&RUN: Improved signal-to-noise ratio over traditional ChIP
ChIP-SICAP: Identifies chromatin-bound protein complexes
HiChIP: Maps long-range chromatin interactions involving ERCC4
Single-Cell Approaches:
scCUT&Tag: Maps ERCC4 binding in individual cells
Single-cell protein analysis: Measures ERCC4 levels in heterogeneous populations
Spatial transcriptomics correlation with ERCC4 localization
Live-Cell Imaging Technologies:
CRISPR-based tagging of endogenous ERCC4
Split-fluorescent protein complementation for interaction visualization
Optogenetic control of ERCC4 recruitment
Integrated Multi-Omics Approaches:
Correlate ERCC4 binding with DNA damage locations
Map repair outcomes at ERCC4-bound sites
Link to transcriptional regulation and chromatin structure
These methodologies address the challenge of studying dynamic, low-abundance repair factors like ERCC4 in their native chromatin context, providing insights into the spatio-temporal organization of DNA repair processes.
ERCC4 antibodies provide valuable tools for investigating repair-aging connections:
Aging-Related ERCC4 Alterations:
Expression level changes during replicative and organismal aging
Post-translational modifications affecting function
Protein-protein interaction dynamics in aged cells
Progeroid Syndrome Research Applications:
Methodological Approaches for Senescence Studies:
| Technique | Application | Measurement Outcome |
|---|---|---|
| Immunofluorescence | Co-localization with senescence markers | Association with persistent DNA damage |
| ChIP-seq | Genome-wide binding changes | Age-related redistribution patterns |
| Protein interaction studies | Co-IP followed by mass spectrometry | Altered repair complex formation |
| Functional repair assays | Unscheduled DNA synthesis, ICL repair | Age-dependent repair capacity |
Intervention Testing Models:
Monitor ERCC4 status during senolytic treatments
Assess impact of caloric restriction on ERCC4 function
Evaluate ERCC4 pathway activation by anti-aging compounds
Translational Applications:
Biomarkers of DNA repair capacity in aging
Therapeutic targets to enhance repair in aged tissues
Predictors of age-related disease susceptibility
Research has demonstrated that ERCC4 mutations can cause accelerated aging phenotypes , making this protein a critical node connecting DNA repair efficiency with aging processes and a valuable target for intervention development.
Highly multiplexed imaging with ERCC4 antibodies requires specialized methodological approaches:
Panel Design Principles:
Include markers for different repair pathways
Add cell cycle phase indicators
Incorporate damage type-specific markers
Cyclic Immunofluorescence Methods:
Sequential staining-imaging-bleaching cycles
Biotin-conjugated ERCC4 antibodies as anchoring markers
Careful validation of epitope stability through cycles
Advanced Imaging Technologies:
| Technology | Advantage | ERCC4 Application |
|---|---|---|
| CODEX | 40+ markers in single sample | Comprehensive repair pathway mapping |
| Imaging Mass Cytometry | 40+ proteins at subcellular resolution | Metal-labeled antibodies for quantitative analysis |
| 4i (iterative immunofluorescence) | Repeated cycles on same sample | Temporal dynamics of repair complex assembly |
| Super-resolution microscopy | Nanoscale resolution | Fine structure of repair foci |
Data Analysis Challenges:
Image registration across cycles
Segmentation of nuclear structures
Quantification of co-localization events
Machine learning for pattern recognition
Validation Requirements:
Single-stain controls for each marker
Spillover compensation matrices
Comparison with orthogonal methods
Reproducibility across experimental conditions
These approaches enable unprecedented insights into the spatial organization of DNA repair processes, revealing how ERCC4 coordinates with other factors in complex repair pathways and how these interactions are altered in disease states.
Integrating antibody-based detection with genomic methods provides powerful insights:
Multi-Modal Data Integration Strategies:
Correlate ERCC4 binding sites (ChIP-seq) with mutation patterns (whole-genome sequencing)
Link protein levels (immunoblot) with expression profiles (RNA-seq)
Connect repair complex formation (IP-MS) with epigenetic landscapes (ATAC-seq)
Sequential Workflow Approaches:
| Genomic Method | Antibody-Based Follow-up | Integrated Insight |
|---|---|---|
| DNA damage mapping | ERCC4 ChIP at damage sites | Repair efficiency correlation |
| CRISPR screens | Immunoblot of pathway components | Compensatory mechanism identification |
| RNA-seq after damage | ERCC4 ChIP-seq in same conditions | Transcription-repair coupling |
| Mutation signature analysis | ERCC4 functional assays | Repair deficiency biomarkers |
Single-Cell Multi-Omics Integration:
Combine protein detection (ERCC4) with transcriptomics
Correlate repair capacity with cellular states
Track clonal evolution of repair-deficient cells
Spatial Biology Applications:
Multiplex imaging with spatial transcriptomics
Map repair centers relative to nuclear architecture
Correlate with 3D genome organization
Computational Framework Requirements:
Data normalization across platforms
Feature selection for cross-modal correlation
Network analysis to identify regulatory relationships
Machine learning integration of multi-modal data
This integrated approach has revealed that ERCC4 functions extend beyond canonical repair roles to include influences on gene expression and chromosome architecture, particularly at sites where transcription and repair pathways intersect.
Comprehensive validation of ERCC4 antibodies should include:
Specificity Verification:
Application-Specific Validation Tests:
Reproducibility Assessment:
Inter-lot comparison
Inter-laboratory validation
Performance in multiple cell types/tissues
Functional Correlation Tests:
Documentation Standards:
Detailed methods for each validation experiment
Raw data preservation and accessibility
Transparent reporting of limitations
These rigorous validation measures ensure reliable research outcomes when using ERCC4 antibodies across multiple experimental systems and applications.
Researchers should adhere to these best practices for transparency and reproducibility:
Comprehensive Antibody Reporting:
Detailed Methodology Documentation:
Complete protocol with all buffer compositions
Incubation conditions (time, temperature, concentration)
Critical steps (blocking, washing stringency)
Image acquisition parameters or flow cytometry settings
Controls Disclosure:
Positive and negative controls used
Validation in relevant experimental system
Supporting data demonstrating specificity
Limitation acknowledgments
Data Presentation Standards:
| Data Type | Required Information | Best Practice |
|---|---|---|
| Western Blot | Full blots with molecular weight markers | Show biologically relevant replicates |
| Immunofluorescence | Raw and processed images | Include scale bars and colocalization metrics |
| Flow Cytometry | Gating strategy and controls | Show both histogram and statistical analysis |
| ChIP data | Input normalization method | Include known targets as positive controls |
Resource Sharing Commitments:
Detailed protocols deposition
Raw data availability statement
Reagent sharing policies
Analysis code/pipeline access
Adherence to these practices enhances research reproducibility and facilitates building upon existing knowledge in ERCC4 biology and DNA repair mechanisms.
Emerging directions in ERCC4 antibody technology include:
Next-Generation Antibody Formats:
Recombinant antibody fragments for improved penetration
Nanobodies for super-resolution imaging applications
Bi-specific antibodies for proximity detection
Conditionally active antibodies for damage-induced detection
Advanced Conjugation Strategies:
Site-specific biotin conjugation for optimal orientation
Click chemistry-compatible antibodies for modular detection
Photoactivatable crosslinkers for capturing transient interactions
Degradation-resistant linkers for long-term imaging
Mutation-Specific Antibody Development:
Antibodies recognizing common pathogenic variants
Conformational-state specific antibodies
Post-translational modification status detection
Functional activity-reporting antibodies
Technological Integration Opportunities:
| Technology | Application to ERCC4 | Potential Impact |
|---|---|---|
| CRISPR-based tagging | Endogenous labeling | Native context visualization |
| Spatial proteomics | Repair complex mapping | Comprehensive pathway organization |
| Deep learning analysis | Pattern recognition in repair foci | Predictive biomarkers |
| Organ-on-chip models | Tissue-specific repair dynamics | Personalized intervention testing |
Translational Development Pathways:
Standardized diagnostic assays
Companion diagnostics for DNA repair-targeted therapies
Screening tools for chemical modulators of ERCC4 function
Non-invasive detection methods for clinical monitoring