TY - JOUR
T1 - Genetic complementation of radiation response by 3′ untranslated regions (UTR) of RNA
AU - Chen, P.
AU - Girjes, A. A.
AU - Hobson, K.
AU - Beamish, H.
AU - Khanna, K. K.
AU - Farrell, A.
AU - Gatei, M.
AU - Teale, B.
AU - Buchwald, M.
AU - Legerski, R.
AU - Lavin, M. F.
N1 - Funding Information:
This work was supported by grants from the National H ealth and Medical Research Council of Australia, the Q ueensland Cancer Fund, a National Institute of Health USA the A-T Chil-drens Project, Boca Raton, FL, and the Buddhist Compassion Relief Tzu-chi A-T Fund, Taiwan. Manual Buchwald was supported by the Medical Research Council of Canada. We wish to thank Ann Knight and Mandie Quince for typing the manuscript.
PY - 1996
Y1 - 1996
N2 - The molecular basis of radiosensitivity was studied using a cDNA complementation approach to correct radio-sensitivity in cells. Four cDNAs of sizes 1·6, 2·0, 2·2 and 2·5 kb were isolated that corrected several aspects of the phenotype of cells from patients with the human genetic disorder ataxia-telangiectasia, characterized by hypersensitivity to ionizing radiation. The criteria used to assess correction included cell viability, induced chromosome aberrations, G2 phase delay and induction of p53 after exposure to radiation. One cDNA (2·5kb) was identified as the complete sequence of the RNA helicase p68, which was capable of correcting radiosensitivity based on two of the above four criteria, with p53 induction post irradiation being partially corrected. The 2·2 kb cDNA was shown to correspond to the complete sequence of arginyl tRNA synthetase and the other two cDNAs were identical to the 3′ untranslated regions (UTR) of the transcription factor TFIIS (1·6kb) and phospholipase A2 (2·0 kb) respectively. Additional transfections with the 3′UTR (198 nucleotides) of p68 RNA helicase and its inverse sequence revealed that the 3′UTR had the same complementation capacity as the full-length cDNA, whereas the inverse construct failed to complement radiosensitivity. These data provide additional support for a novel role for 3′UTRs in the regulation of gene expression.
AB - The molecular basis of radiosensitivity was studied using a cDNA complementation approach to correct radio-sensitivity in cells. Four cDNAs of sizes 1·6, 2·0, 2·2 and 2·5 kb were isolated that corrected several aspects of the phenotype of cells from patients with the human genetic disorder ataxia-telangiectasia, characterized by hypersensitivity to ionizing radiation. The criteria used to assess correction included cell viability, induced chromosome aberrations, G2 phase delay and induction of p53 after exposure to radiation. One cDNA (2·5kb) was identified as the complete sequence of the RNA helicase p68, which was capable of correcting radiosensitivity based on two of the above four criteria, with p53 induction post irradiation being partially corrected. The 2·2 kb cDNA was shown to correspond to the complete sequence of arginyl tRNA synthetase and the other two cDNAs were identical to the 3′ untranslated regions (UTR) of the transcription factor TFIIS (1·6kb) and phospholipase A2 (2·0 kb) respectively. Additional transfections with the 3′UTR (198 nucleotides) of p68 RNA helicase and its inverse sequence revealed that the 3′UTR had the same complementation capacity as the full-length cDNA, whereas the inverse construct failed to complement radiosensitivity. These data provide additional support for a novel role for 3′UTRs in the regulation of gene expression.
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U2 - 10.1080/095530096145940
DO - 10.1080/095530096145940
M3 - Article
C2 - 8613688
AN - SCOPUS:0029972581
SN - 0955-3002
VL - 69
SP - 385
EP - 395
JO - International journal of radiation biology
JF - International journal of radiation biology
IS - 3
ER -