Inhibition of DNA Synthesis by Ionizing Radiation

  • Nicolaas G. J. Jaspers
  • Malgorzata Z. Zdzienicka
Part of the Methods in Molecular Biology™ book series (MIMB, volume 113)


In mammalian cells, the rate of DNA synthesis decreases after X-ray exposure. The dose-response curve indicates a biphasic kinetics of inhibition (see Fig. 1). The initial, steep component of the curve represents inhibition of initiation of new replicons, whereas the shallow component is a manifestation of chain growth failure. The latter is probably owing to direct interference by DNA lesions with the replication machinery; on the other hand, slowdown of replicon initiation is one of the manifestations of an active signal-mediated response. Evidence for this was obtained from studies on cells derived from patients with the autosomal-recessive human diseases ataxia telangiectasia (AT) and Nijmegen Breakage Syndrome (NBS), and on some laboratory-generated radiosensitive rodent cell lines (1,2). AT and NBS cells have virtually lost the steep component of the inhibition curve. This property is usually referred to as “radioresistant DNA synthesis” (RDS), a phrase originally coined by Painter (3). In the rodent mutants, diminished replicon initiation is also evident, but the degree of DNA synthesis inhibition is generally lower in the parental hamster cell lines as well (4,5).
Fig. 1.

Inhibition of DNA replication by ionizing radiation in primary human fibroblasts. Left, dose-response curve measured in the first 3 h after exposure. Right, timecourse after exposure to 20 Gy of γ-rays. (Measured with 30-min labeling pulses).


Ataxia Telangiectasia Ataxia Telangiectasia Inhibition Curve Nijmegen Breakage Syndrome Cockayne Syndrome 
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Copyright information

© Humana Press Inc. 1999

Authors and Affiliations

  • Nicolaas G. J. Jaspers
  • Malgorzata Z. Zdzienicka

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