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

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    13 Citations (Scopus)

    Abstract

    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.

    Original languageEnglish
    Pages (from-to)743-748
    Number of pages6
    JournalCARCINOGENESIS
    Volume16
    Issue number4
    Publication statusPublished - Apr-1995

    Keywords

    • CYCLOBUTANE PYRIMIDINE DIMERS
    • ADENOSINE-DEAMINASE GENE
    • STRAND-BREAK REPAIR
    • DNA-REPAIR
    • MAMMALIAN-CELLS
    • IONIZING-RADIATION
    • COCKAYNE-SYNDROME
    • NUCLEAR MATRIX
    • CHO CELLS
    • DHFR GENE

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