PMID: 6403035Jan 20, 1983Paper

Effect of aphidicolin on de novo DNA synthesis, DNA repair and cytotoxicity in gamma-irradiated human fibroblasts. Implications for the enhanced radiosensitivity in ataxia telangiectasia

Biochimica Et Biophysica Acta
P J Smith, M C Paterson

Abstract

The antibiotic, aphidicolin, is a potent inhibitor of DNA polymerase alpha and consequently of de novo DNA synthesis in human cells. We report here that in gamma-irradiated normal human cells, aphidicolin (at 5 micrograms/ml and less) had no significant effect on the rate of the rejoining of DNA single strand breaks or rate of removal of DNA lesions assayed as sites sensitive to incising activities present in crude protein extracts of Micrococcus luteus cells. gamma-irradiated human ataxia telangiectasia cells are known to demonstrate enhanced cell killing and exhibit resistance to the inhibiting effects of radiation on DNA synthesis. Under conditions of minimal aphidicolin cytotoxicity but extensive inhibition of de novo DNA synthesis, the radiation responses of neither normal nor ataxia telangiectasia cells were significantly modified by aphidicolin. Firstly, we conclude that human DNA polymerase alpha is not primarily involved in the repair of the two classes of radiogenic DNA lesions examined. Secondly, the radiation hypersensitivity of ataxia telangiectasia cells cannot be explained on the basis of premature replication of damaged cellular DNA resulting from the resistance of de novo DNA synthesis to inhibition by ionizing...Continue Reading

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Citations

Mar 1, 1989·Mutation Research·N S Rudolph, S A Latt
May 1, 1988·Mutation Research·M F Lavin, A L Schroeder
Jun 6, 1995·Proceedings of the National Academy of Sciences of the United States of America·D W RussellA D Miller
Feb 1, 1988·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·I R Radford, S Broadhurst
May 1, 1996·International Journal of Radiation Biology·T J Jorgensen, Y Shiloh
Mar 29, 1996·The Journal of Biological Chemistry·O S BangM C Birchenall-Roberts
Jan 1, 1984·Journal of Cellular Physiology. Supplement·M C PatersonM Weinfeld
Jun 1, 1985·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·P J SmithJ V Watson
May 1, 1989·Human Genetics·B R Young, R B Painter
Jan 1, 1989·International Journal of Radiation Biology·H Mozdarani, P E Bryant
Apr 1, 1986·International Journal of Radiation Biology and Related Studies in Physics, Chemistry, and Medicine·A R LehmannJ E Lowe
Jan 1, 1987·Progress in Biophysics and Molecular Biology·A M George, W A Cramp

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