Down-regulation of the human CDC16 gene after exposure to ionizing radiation: a possible role in the radioadaptive response.
We have used the method of differential display of mRNAs to search for changes in gene expression associated with radioadaptation triggered by low doses of ionizing radiation in human lymphoblasts. We isolated a cDNA designated PB13 that was down-regulated as early as 1 h after irradiation with 4 Gy in cells adapted by a pre-exposure to a dose of 2 cGy, compared to 3 h in nonadapted cells (4 Gy alone). Northern analysis confirmed the differential expression of a 2.4-kb transcript that was repressed for at least 10 h after irradiation. The major part of the PB13 cDNA was identical to the human CDC16 mRNA. When using either PB13 or CDC16 cDNA as probes, similar radiation-induced alterations in gene expression were observed. Expression of the CDC16 gene was also repressed after oxidative stress with H(2)O(2). The CDC16 protein belongs to the anaphase-promoting complex (APC) that controls progression through mitosis. The repression of expression of the CDC16 gene by ionizing radiation could result in delayed progression of damaged cells through mitosis. This cycle delay would occur earlier in adapted cells and would allow a more rapid and efficient repair that could contribute to the tolerance to subsequent irradiation.
Zhou
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Institut Curie-Recherche, UMR 218 CNRS, 26 rue d'Ulm, 75241 Paris cedex 05, France and INRA-CEA, DSV/DRRILREG, 78352 Jouy en Josas cedex, France.
Rigaud
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D000220:Adaptation, Biological / Q000235:genetics; D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; D001483:Base Sequence; D002453:Cell Cycle / Q000528:radiation effects; D018797:Cell Cycle Proteins / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D018076:DNA, Complementary / Q000235:genetics; D015536:Down-Regulation / Q000528:radiation effects*; D020869:Gene Expression Profiling; D006801:Humans; D008214:Lymphocytes / Q000166:cytology / Q000378:metabolism / Q000528:radiation effects; D008938:Mitosis / Q000528:radiation effects; D008969:Molecular Sequence Data; D011836:Radiation Tolerance / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid
D064194:Apc6 Subunit, Anaphase-Promoting Complex-Cyclosome; C577395:CDC16 protein, human; D018797:Cell Cycle Proteins; D018076:DNA, Complementary