ArticleNucleic acids research2003
Modification of the ionizing radiation response in living cells by an scFv against the DNA-dependent protein kinase.
Article in Nucleic acids research, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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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.
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Who cites it
12 citing papers in PubMed, 26 citations in OpenAlex.
- Small Cajal body-associated RNA 2 (scaRNA2) regulates DNA repair pathway choice by inhibiting DNA-PK.Nature communications · 2022Article
- BRCA1 modulates the autophosphorylation status of DNA-PKcs in S phase of the cell cycle.Nucleic acids research · 2014Article
- Genotypic characteristics of resistant tumors to pre-operative ionizing radiation in rectal cancer.World journal of gastrointestinal oncology · 2014Review
- Intranuclear delivery of a novel antibody-derived radiosensitizer targeting the DNA-dependent protein kinase catalytic subunit.International journal of radiation oncology, biology, physics · 2012Article
- Role of DNA-dependent protein kinase catalytic subunit in cancer development and treatment.Translational cancer research · 2012Article
- The NF90/NF45 complex participates in DNA break repair via nonhomologous end joining.Molecular and cellular biology · 2011Article
- Radiosensitization and growth inhibition of cancer cells mediated by an scFv antibody gene against DNA-PKcs in vitro and in vivo.Radiation oncology (London, England) · 2010Article
- Porous-wall hollow glass microspheres as novel potential nanocarriers for biomedical applications.Nanomedicine : nanotechnology, biology, and medicine · 2010Article
- E. coli expression of a soluble, active single-chain antibody variable fragment containing a nuclear localization signal.Protein expression and purification · 2009Article
- Identification and biological evaluation of a novel and potent small molecule radiation sensitizer via an unbiased screen of a chemical library.Cancer research · 2007Article
- Modifying the function of DNA repair nanomachines for therapeutic benefit.Nanomedicine : nanotechnology, biology, and medicine · 2006Article
- The life and death of DNA-PK.Oncogene · 2005Review
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 1 institution in 1 country.
Funding
Abstract
The non-homologous end joining pathway uses pre-existing proteins to repair DNA double-strand breaks induced by ionizing radiation. Here we describe manipulation of this pathway in living cells using a newly developed tool. We generated a single chain antibody variable fragment (scFv) that binds to the DNA-dependent protein kinase catalytic subunit (DNA-PKcs), a key enzyme in the pathway. In contrast to existing pharmacologic inhibitors, the scFv binds a newly defined regulatory site outside the kinase catalytic domain. Although the scFv inhibits kinase activity only modestly, it completely blocks DNA end joining in a cell-free system. Microinjection of the scFv sensitizes human cells to radiation, as measured by a reduction in efficiency of colony formation and induction of apoptosis at an otherwise sublethal dose of 1.5 Gy. The scFv blocks non-homologous end joining in situ at a step subsequent to histone gamma-H2AX focus formation but preceding gamma-H2AX dephosphorylation. Blockage occurs in cells exposed to as little as 0.1 Gy, indicating that DNA-PKcs is essential for double-strand break repair even at low radiation doses. The ability to modify the radiation response in situ in living cells provides a link between biochemical, genetic and cytologic approaches to the study of double-strand break repair intermediates.
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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.