ArticleInternational journal of radiation oncology, biology, physics2019
Characterisation of Deubiquitylating Enzymes in the Cellular Response to High-LET Ionizing Radiation and Complex DNA Damage.
Article in International journal of radiation oncology, biology, physics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
27 citing papers in PubMed, 35 citations in OpenAlex.
- Understanding and Exacerbating the Biological Response of Uveal Melanoma to Proton Beam Therapy.Cancers · 2025Review
- Radiobiological characterisation of a 28 MeV proton beam delivered by the MC-40 cyclotron.Cell death discovery · 2025Article
- Potential Benefits of Combining Proton or Carbon Ion Therapy with DNA Damage Repair Inhibitors.Cells · 2024Review
- Targeting OGG1 and PARG radiosensitises head and neck cancer cells to high-LET protons through complex DNA damage persistence.Cell death & disease · 2024Article
- KH-like Domains in PARP9/DTX3L and PARP14 Coordinate Protein-Protein Interactions to Promote Cancer Cell Survival.Journal of molecular biology · 2024Article
- DNA damage and repair dependencies of ionising radiation modalities.Bioscience reports · 2023Review
- Nanodrugs with intrinsic radioprotective exertion: Turning the double-edged sword into a single-edged knife.Exploration (Beijing, China) · 2023Review
- The Cellular Response to Complex DNA Damage Induced by Ionising Radiation.International journal of molecular sciences · 2023Review
- DNA Damage Response Mechanisms in Head and Neck Cancer: Significant Implications for Therapy and Survival.International journal of molecular sciences · 2023Review
- Overcoming the Impact of Hypoxia in Driving Radiotherapy Resistance in Head and Neck Squamous Cell Carcinoma.Cancers · 2022Review
- DNA Damage Clustering after Ionizing Radiation and Consequences in the Processing of Chromatin Breaks.Molecules (Basel, Switzerland) · 2022Review
- Effectiveness of PARP inhibition in enhancing the radiosensitivity of 3D spheroids of head and neck squamous cell carcinoma.Frontiers in oncology · 2022Article
- MicroRNA: a novel implication for damage and protection against ionizing radiation.Environmental science and pollution research international · 2021Review
- The Enzyme-Modified Neutral Comet (EMNC) Assay for Complex DNA Damage Detection.Methods and protocols · 2021Article
- Review
- The Biological Basis for Enhanced Effects of Proton Radiation Therapy Relative to Photon Radiation Therapy for Head and Neck Squamous Cell Carcinoma.International journal of particle therapy · 2021Article
- DNA Double Strand Break Repair Pathways in Response to Different Types of Ionizing Radiation.Frontiers in genetics · 2021Review
- USP9X Is Required to Maintain Cell Survival in Response to High-LET Radiation.Frontiers in oncology · 2021Article
- Article
- FLASH Radiotherapy: Current Knowledge and Future Insights Using Proton-Beam Therapy.International journal of molecular sciences · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 1 country.
Funding
Abstract
purposeIonizing radiation, particular high-linear energy transfer (LET) radiation, can induce complex DNA damage (CDD) wherein 2 or more DNA lesions are induced in close proximity, which contributes significantly to the cell killing effects. However, knowledge of the enzymes and mechanisms involved in coordinating the recognition and processing of CDD in cellular DNA are currently lacking. METHODS AND MATERIALS: A small interfering RNA screen of deubiquitylation enzymes was conducted in HeLa cells irradiated with high-LET α-particles or protons, versus low-LET protons and x-rays, and cell survival was monitored by clonogenic assays. Candidates whose depletion led to decreased cell survival specifically in response to high-LET radiation were validated in both HeLa and oropharyngeal squamous cell carcinoma (UMSCC74A) cells, and the association with CDD repair was confirmed using an enzyme modified neutral comet assay.
resultsDepletion of USP6 decreased cell survival specifically after high-LET α-particles and protons, but not low-LET protons or x-rays. USP6 depletion caused cell cycle arrest and a deficiency in CDD repair mediated through instability of poly(ADP-ribose) polymerase-1 (PARP-1) protein. Increased radiosensitivity of cells to high-LET protons as a consequence of defective CDD repair was furthermore mimicked using the PARP inhibitor olaparib, and through PARP-1 small interfering RNA.
conclusionsUSP6 controls cell survival in response to high-LET radiation by stabilizing PARP-1 protein levels, which is essential for CDD repair. We also describe synergy between CDD induced by high-LET protons and PARP inhibition, or PARP-1 depletion, in effective cancer cell killing.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.