GO:0072719 cellular response to cisplatin: DNA Damage Response Pathway, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0072719 (cellular response to cisplatin) describes any change in a cell's state or activity caused by cisplatin, including DNA damage signaling, gene expression changes, and cell death decisions.
• Cisplatin binds cellular DNA to form platinum-DNA adducts, and the kinetics of this binding can be modulated by thiol-blocking agents and thiol drugs.
• The cellular response to cisplatin involves DNA repair, apoptosis, senescence, and stress signaling, with proteins such as DNA polymerase beta and NPEPPS influencing sensitivity.
• Cisplatin sensitivity can be regulated by kinases such as PKMYT1 and by immune signaling pathways such as STING.
• Cisplatin-induced cellular senescence and fibrosis can be modeled in human kidney tubuloids for drug screening.
• Cisplatin response can be studied by confocal Raman microspectroscopy, which detects cellular changes in osteosarcoma cells.
Description
Cisplatin is a platinum-based chemotherapeutic agent widely used to treat solid tumors, and its interaction with cells triggers a complex biological process captured by the Gene Ontology term GO:0072719, cellular response to cisplatin. This term is defined as any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cisplatin stimulus. Understanding this response is critical because it determines whether a cancer cell survives, repairs damage, or dies, and it underlies mechanisms of drug resistance and toxicity. The cellular response to cisplatin begins with drug uptake and DNA binding, forming platinum-DNA adducts that distort the double helix and activate DNA damage recognition pathways. These initial events lead to a cascade of signaling and transcriptional changes that can culminate in apoptosis, senescence, or survival, depending on cellular context and genetic background. Research into GO:0072719 spans cancer biology, nephrotoxicity, and drug discovery, with studies using osteosarcoma, breast cancer, and kidney models to dissect the molecular players involved. This article integrates authoritative QuickGO annotation with verified PubMed literature to provide a research-grade overview of the genes, functions, and methods associated with cellular response to cisplatin.
cellular response to cisplatin At A Glance
| GO ID | GO:0072719 |
|---|---|
| GO term | cellular response to cisplatin |
| Ontology | biological_process |
| Synonym | none |
| Major function | Cellular response to cisplatin stimulus, including DNA damage signaling, gene expression changes, and cell fate decisions |
| Definition | Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cisplatin stimulus. |
| Related processes | DNA damage response, apoptosis, senescence, stress signaling |
| Key molecular players | DNA polymerase beta, NPEPPS, PKMYT1, STING pathway components |
| Research models | Osteosarcoma, triple-negative breast cancer, kidney tubuloids |
What Is GO:0072719?
GO:0072719, cellular response to cisplatin, is a biological process term defined as any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cisplatin stimulus. In other words, it encompasses all cellular reactions triggered by exposure to cisplatin, from immediate DNA damage sensing to long-term changes in gene expression, cell cycle progression, and cell fate decisions such as apoptosis or senescence.
Why Is cellular response to cisplatin Important in Cell Biology?
The cellular response to cisplatin is central to cancer chemotherapy efficacy and toxicity. It determines whether tumor cells survive treatment or undergo cell death, and its dysregulation contributes to platinum resistance, a major clinical challenge. Moreover, cisplatin-induced cellular senescence and fibrosis in kidney cells can lead to nephrotoxicity, limiting its clinical use. Understanding GO:0072719 helps researchers identify biomarkers of response, develop combination therapies, and design safer cisplatin-based regimens.
• Cisplatin is a first-line chemotherapy for many solid tumors, and cellular response determines therapeutic outcome.
• Platinum resistance is a major cause of treatment failure, driven by alterations in cellular response pathways.
• DNA repair proteins such as DNA polymerase beta modulate cisplatin sensitivity.
• Kinases like PKMYT1 can ameliorate cisplatin sensitivity in osteosarcoma.
• Immune signaling via STING can potentiate cisplatin sensitivity in triple-negative breast cancer.
• Cisplatin-induced senescence and fibrosis in kidney tubuloids model nephrotoxicity.
• Cellular response to cisplatin can be monitored by confocal Raman microspectroscopy.
• Cisplatin binding to DNA is modulated by thiol-blocking agents and thiol drugs.
• Cisplatin resistance can affect cellular radiation response.
What Happens During cellular response to cisplatin?
Cisplatin uptake and DNA binding
In simple terms: Cisplatin enters the cell and attaches to DNA, causing damage.
Cisplatin is taken up by cells and undergoes aquation, becoming reactive and binding to DNA, primarily at guanine N7 positions, to form platinum-DNA adducts. The kinetics of cisplatin binding to cellular DNA can be modulated by thiol-blocking agents and thiol drugs, indicating that intracellular thiols influence adduct formation. These adducts distort DNA structure and are recognized by cellular damage sensors.
DNA damage recognition and signaling
In simple terms: The cell detects DNA damage and sends signals to repair or die.
Platinum-DNA adducts activate DNA damage response pathways, including ATM/ATR kinases, which phosphorylate downstream targets to halt cell cycle progression and initiate repair. DNA polymerase beta, a key repair enzyme, can influence cellular response to cisplatin; germline variants in DNA polymerase beta confer altered cellular response to cisplatin therapy. This signaling determines whether the cell attempts repair or commits to apoptosis.
Apoptosis and cell death
In simple terms: If damage is too severe, the cell triggers its own death.
When DNA damage is irreparable, cells activate apoptosis through p53-dependent and independent pathways. The cellular response to cisplatin often culminates in apoptosis, which is the desired outcome in cancer therapy. However, cancer cells can evade apoptosis, leading to resistance. For example, PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma, suggesting that inhibition of this kinase could enhance apoptosis.
Senescence and fibrosis
In simple terms: Some cells stop dividing permanently and cause tissue scarring.
Cisplatin can induce cellular senescence, a state of permanent growth arrest, in kidney tubular cells. Repeated cisplatin exposure in human kidney tubuloids leads to senescence and fibrosis, modeling chronic nephrotoxicity. This response is distinct from apoptosis and contributes to long-term tissue damage.
Immune and stress signaling
In simple terms: The cell's stress and immune alarms can make cisplatin more effective.
Cisplatin-induced DNA damage can activate the STING pathway, which triggers interferon responses and enhances anti-tumor immunity. Astragaloside IV potentiates cisplatin sensitivity in triple-negative breast cancer via STING signaling pathway activation. This highlights crosstalk between DNA damage response and innate immune signaling in the cellular response to cisplatin.
Key Genes Involved in GO:0072719 cellular response to cisplatin
The following genes and proteins have been experimentally implicated in the cellular response to cisplatin, based on verified PubMed literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| PKMYT1 | Kinase that ameliorates cisplatin sensitivity | Target for enhancing cisplatin efficacy in osteosarcoma |
| NPEPPS | Druggable driver of platinum resistance | Potential target to overcome resistance |
| POLB | DNA polymerase beta, involved in base excision repair | Germline variant confers cellular response to cisplatin |
| STING1 | Stimulator of interferon genes, immune signaling | Activation potentiates cisplatin sensitivity in breast cancer |
| TP53 | Tumor suppressor, regulates apoptosis and senescence | Frequently mutated in cancers, affects cisplatin response |
| ATM | DNA damage sensor kinase | Coordinates DNA repair and cell cycle arrest |
| ATR | DNA damage sensor kinase | Responds to replication stress induced by cisplatin |
| ERCC1 | Nucleotide excision repair protein | Involved in repair of platinum-DNA adducts |
| XPF | Nucleotide excision repair endonuclease | Works with ERCC1 in adduct removal |
| BAX | Pro-apoptotic Bcl-2 family member | Mediates cisplatin-induced apoptosis |
| BCL2 | Anti-apoptotic protein | Overexpression can cause cisplatin resistance |
| CASP3 | Executioner caspase | Cleaves substrates during apoptosis |
| CASP9 | Initiator caspase | Activates intrinsic apoptosis pathway |
| CDKN1A | p21, cell cycle inhibitor | Induced by p53 upon cisplatin damage |
| MAPK1 | ERK2, stress-activated kinase | Modulates survival signaling |
| MAPK3 | ERK1, stress-activated kinase | Modulates survival signaling |
| RELA | NF-kB subunit | Regulates survival genes in response to cisplatin |
| IFNB1 | Interferon beta | Produced upon STING activation |
How Is cellular response to cisplatin Regulated?
The cellular response to cisplatin is regulated at multiple levels. DNA damage sensors ATM and ATR initiate signaling cascades that activate checkpoint kinases, leading to cell cycle arrest and repair. The p53 tumor suppressor is a key transcription factor that regulates genes involved in apoptosis, senescence, and DNA repair. Kinases such as PKMYT1 can modulate sensitivity by affecting cell cycle progression. Additionally, the STING pathway links DNA damage to immune signaling, and its activation can enhance cisplatin sensitivity. Thiol-containing compounds can modulate cisplatin binding to DNA, affecting the initial damage load.
cellular response to cisplatin and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| PKMYT1 | Osteosarcoma cisplatin sensitivity | Knockout or overexpression in osteosarcoma cell lines |
| NPEPPS | Platinum resistance in cancer | CRISPR knockout in resistant cell lines |
| POLB | Cisplatin response in cancer | Point mutation knock-in of germline variant |
| STING1 | Triple-negative breast cancer | Overexpression or knockout in breast cancer cells |
| CDKN1A | Kidney fibrosis and senescence | Kidney tubuloid model with repeated cisplatin |
Cancer and platinum resistance
The cellular response to cisplatin is directly linked to chemotherapy outcome in cancers such as osteosarcoma, triple-negative breast cancer, and ovarian cancer. Resistance mechanisms include enhanced DNA repair, altered apoptosis, and increased drug efflux. NPEPPS has been identified as a druggable driver of platinum resistance, and targeting it could restore sensitivity. PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma, suggesting that its inhibition may overcome resistance. In triple-negative breast cancer, activation of STING signaling by Astragaloside IV potentiates cisplatin sensitivity.
Nephrotoxicity and kidney fibrosis
Cisplatin is nephrotoxic, causing acute kidney injury and chronic fibrosis. Repeated cisplatin exposure induces cellular senescence in kidney tubular cells, leading to fibrosis. A human kidney tubuloid model of repeated cisplatin-induced cellular senescence and fibrosis has been developed for drug screening, providing a platform to study this aspect of the cellular response.
DNA repair defects and personalized therapy
Germline variants in DNA repair genes such as POLB can alter cellular response to cisplatin. A DNA polymerase beta germline variant confers cellular response to cisplatin therapy, highlighting the potential for pharmacogenomic approaches to personalize cisplatin treatment.
Radiation response and combination therapy
Cisplatin resistance can affect cellular radiation response, with implications for combined chemoradiotherapy. Studies in cell models have shown that cisplatin-resistant cells may exhibit altered radiosensitivity, informing treatment scheduling.
From cellular response to cisplatin-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X affect cisplatin sensitivity? | CRISPR knockout cell line followed by cisplatin dose-response |
| Does a specific point mutation in POLB alter cisplatin response? | Point mutation knock-in using CRISPR |
| Can overexpression of STING enhance cisplatin sensitivity? | Overexpression cell model in triple-negative breast cancer |
| Does tagging a DNA repair protein affect its localization after cisplatin? | Tagged knock-in with fluorescent tag |
| Does NPEPPS knockout reverse platinum resistance? | CRISPR knockout in resistant cancer cell lines |
| Does repeated cisplatin induce senescence in kidney cells? | Human kidney tubuloid model |
How to Study the cellular response to cisplatin Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Confocal Raman microspectroscopy | Biochemical changes in cells | Label-free monitoring of cisplatin response |
| DNA adduct assay | Platinum-DNA adduct formation | Quantifying initial damage and modulation by thiols |
| Senescence-associated beta-galactosidase | Cellular senescence | Kidney tubuloid model of cisplatin toxicity |
| CRISPR knockout screen | Gene essentiality for cisplatin sensitivity | Identifying resistance genes |
| RNA sequencing | Transcriptional changes | Pathway analysis after cisplatin treatment |
| Western blot | Protein expression and phosphorylation | DNA damage signaling activation |
| Apoptosis assay (caspase 3/7) | Cell death | Evaluating cisplatin-induced apoptosis |
| Clonogenic survival assay | Reproductive cell death | Measuring cisplatin sensitivity |
Confocal Raman microspectroscopy
Confocal Raman microspectroscopy can detect cellular responses to cisplatin by measuring biochemical changes in osteosarcoma cells without labels. This method provides a fingerprint of cellular components and has been used to investigate the cellular responses of osteosarcoma to cisplatin.
DNA adduct quantification
The kinetics of cisplatin binding to cellular DNA can be measured using atomic absorption spectroscopy or immunodetection of platinum-DNA adducts. Thiol-blocking agents and thiol drugs can modulate this binding, and such assays help quantify the initial damage load.
Senescence and fibrosis assays
Cisplatin-induced senescence can be assessed by senescence-associated beta-galactosidase staining, and fibrosis by collagen deposition in kidney tubuloids. This model allows drug screening for compounds that mitigate nephrotoxicity.
CRISPR screening and transcriptomics
Genome-wide CRISPR knockout screens can identify genes that modulate cisplatin sensitivity. RNA sequencing after cisplatin treatment reveals transcriptional changes, and bioinformatics analysis can uncover pathways involved in the cellular response.
How CRISPR Can Be Used to Study GO:0072719 cellular response to cisplatin
Knockout
CRISPR knockout is used to delete genes such as PKMYT1 or NPEPPS to determine their role in cisplatin sensitivity. For example, knockout of PKMYT1 may enhance cisplatin sensitivity in osteosarcoma cells, and knockout of NPEPPS may reverse platinum resistance.
Point Mutation
Point mutation knock-in can model germline variants such as those in POLB that confer altered cellular response to cisplatin. This allows precise study of how a single amino acid change affects DNA repair and drug sensitivity.
Knock-in
Knock-in of tagged proteins, such as fluorescently tagged DNA repair factors, enables real-time imaging of their recruitment to cisplatin-induced DNA damage sites. This provides spatial and temporal insights into the cellular response.
Overexpression
Overexpression of genes such as STING1 can potentiate cisplatin sensitivity by activating immune signaling. Overexpression models help validate gain-of-function effects and identify synergistic drug combinations.
How EDITGENE Supports cellular response to cisplatin Research
Researchers studying cellular response to cisplatin-related genes often need to determine whether a candidate gene is causally involved in drug sensitivity, DNA repair, or cell death. EDITGENE provides a comprehensive suite of CRISPR-based services to enable such investigations, from knockout to precise point mutations and overexpression, supported by library screening and bioinformatics.
Contact EDITGENE today to design your custom CRISPR model for cellular response to cisplatin research.
Frequently Asked Questions About cellular response to cisplatin
What is GO:0072719 cellular response to cisplatin?
GO:0072719 is a Gene Ontology biological process term defined as any process that results in a change in state or activity of a cell as a result of a cisplatin stimulus, including DNA damage signaling, gene expression changes, and cell death.
What genes are involved in cellular response to cisplatin?
Key genes include PKMYT1, NPEPPS, POLB, STING1, TP53, ATM, ATR, and ERCC1, among others, as identified in studies on cisplatin sensitivity and resistance.
How does cisplatin cause DNA damage?
Cisplatin binds to DNA, primarily at guanine N7 positions, forming platinum-DNA adducts that distort the double helix and activate DNA damage response pathways.
What is the role of PKMYT1 in cisplatin sensitivity?
PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma, meaning its inhibition or knockout can enhance cisplatin-induced cell death.
How does NPEPPS contribute to platinum resistance?
NPEPPS is a druggable driver of platinum resistance; targeting it can restore sensitivity to cisplatin in resistant cancers.
Can cisplatin induce senescence in kidney cells?
Yes, repeated cisplatin exposure induces cellular senescence and fibrosis in human kidney tubuloids, modeling nephrotoxicity.
What is the STING pathway's role in cisplatin response?
Activation of STING signaling potentiates cisplatin sensitivity in triple-negative breast cancer by triggering immune responses.
How can CRISPR be used to study cellular response to cisplatin?
CRISPR knockout, point mutation knock-in, and overexpression models allow researchers to test the causal role of specific genes in cisplatin sensitivity and resistance.
What methods are used to measure cellular response to cisplatin?
Methods include confocal Raman microspectroscopy, DNA adduct assays, senescence assays, CRISPR screens, RNA sequencing, and apoptosis assays.
Does cisplatin resistance affect radiation response?
Yes, studies have shown that cisplatin resistance can alter cellular radiation response, which has implications for combined chemoradiotherapy.
Conclusion
GO:0072719 cellular response to cisplatin is a complex biological process that integrates DNA damage sensing, repair, apoptosis, senescence, and immune signaling. Understanding the genes and mechanisms involved is essential for improving cancer therapy and mitigating toxicity. The verified literature highlights key players such as PKMYT1, NPEPPS, POLB, and STING1, and provides models from osteosarcoma to kidney tubuloids. EDITGENE offers a full range of CRISPR services to help researchers dissect these pathways and develop new therapeutic strategies.
References
- 1. Liu B et al.. 2025. PKMYT1 kinase ameliorates cisplatin sensitivity in osteosarcoma.. Signal Transduct Target Ther 10(1):165 PMID: 40393983
- 2. Nakao Y et al.. 2026. A Human Kidney Tubuloid Model of Repeated Cisplatin-Induced Cellular Senescence and Fibrosis for Drug Screening.. Adv Healthc Mater 15(7):e01795 PMID: 41069120
- 3. Bai B et al.. 2025. Astragaloside IV potentiates cisplatin sensitivity in triple-negative breast cancer via STING signaling pathway activation.. Phytomedicine 148:157330 PMID: 41016300
- 4. Wang H et al.. 2022. Investigating the cellular responses of osteosarcoma to cisplatin by confocal Raman microspectroscopy.. J Photochem Photobiol B 226:112366 PMID: 34826719
- 5. Jones RT et al.. 2024. NPEPPS Is a Druggable Driver of Platinum Resistance.. Cancer Res 84(10):1699-1718 PMID: 38535994
- 6. Nemec AA et al.. 2017. DNA Polymerase Beta Germline Variant Confers Cellular Response to Cisplatin Therapy.. Mol Cancer Res 15(3):269-280 PMID: 28074003
- 7. Sadowitz PD et al.. 2002. Kinetics of cisplatin binding to cellular DNA and modulations by thiol-blocking agents and thiol drugs.. Drug Metab Dispos 30(2):183-90 PMID: 11792689
- 8. Wallner KE et al.. 1987. Effect of cisplatin resistance on cellular radiation response.. Int J Radiat Oncol Biol Phys 13(4):587-91 PMID: 3549648
