Selective inhibition of repair of active genes by hyperthermia is due to inhibition of global and transcription coupled repair pathways

Hyperthermia specifically inhibits the repair of UV-induced DNA photolesions in transcriptionally active genes. To define more precisely which mechanisms underlie the heatinduced inhibition of repair of active genes, removal of cyclobutane pyrimidine dimers (CPDs) was studied in human fibroblasts wi...

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Bibliographic Details
Published in:Carcinogenesis (New York) 1995-04, Vol.16 (4), p.743-748
Main Authors: Sakkers, Ron J., Filon, A.Ronald, Brunsting, Jeanette F., Kampinga, Harm H., Konings, Antonius W.T., Mullenders, Leon H.F.
Format: Article
Language:English
Subjects:
Adenosine Deaminase - genetics
Biological and medical sciences
Cell Line
DNA - genetics
DNA - metabolism
DNA Damage
DNA Repair - genetics
Fibroblasts - metabolism
Fibroblasts - physiology
Fibroblasts - radiation effects
Gene Expression Regulation
Humans
Hyperthermia, Induced - adverse effects
Induced hyperthermia. Cryotherapy
Medical sciences
Phenotype
Pyrimidine Dimers - metabolism
RNA - biosynthesis
Severe Combined Immunodeficiency - enzymology
Severe Combined Immunodeficiency - genetics
Transcription, Genetic
Treatment with physical agents
Treatment. General aspects
Tumors
Ultraviolet Rays
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Summary:Hyperthermia specifically inhibits the repair of UV-induced DNA photolesions in transcriptionally active genes. To define more precisely which mechanisms underlie the heatinduced inhibition of repair of active genes, removal of cyclobutane pyrimidine dimers (CPDs) was studied in human fibroblasts with different repair capacities and different transcriptional status of the adenosine deaminase gene, i.e. normal human cells, human cells carrying an inactive copy of the adenosine deaminase gene and xeroderma pigmentosum complementation group C fibroblasts. The results indicate that repair of active genes is impaired by inhibition of two repair pathways: (i) a global repair system involved in the repair of CPDs in potentially active genes; and (ii) the transcription-coupled repair pathway responsible for the accelerated repair of the transcribed strand. Since X-ray-induced DNA damage is also preferentially removed from the transcribed strand of active genes, selective inhibition of repair of radiation-induced DNA damage in active genes may play a key role in radiosensitization due to hyperthermia.
ISSN:0143-3334
1460-2180
DOI:10.1093/carcin/16.4.743