SELECTIVE-INHIBITION OF REPAIR OF ACTIVE GENES BY HYPERTHERMIA IS DUE TO INHIBITION OF GLOBAL AND TRANSCRIPTION COUPLED REPAIR PATHWAYS

RJ SAKKERS*, AR FILON, JF BRUNSTING, HH KAMPINGA, AWT KONINGS, LHF MULLENDERS

*Bijbehorende auteur voor dit werk

    OnderzoeksoutputAcademicpeer review

    13 Citaten (Scopus)

    Samenvatting

    Hyperthermia specifically inhibits the repair of UV-induced DNA photolesions in transcriptionally active genes, To define more precisely which mechanisms underlie the heat-induced 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.

    Originele taal-2English
    Pagina's (van-tot)743-748
    Aantal pagina's6
    TijdschriftCARCINOGENESIS
    Volume16
    Nummer van het tijdschrift4
    StatusPublished - apr-1995

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