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DNA Replication in Mammalian Cells Damaged by Mutagens

  • Alan R. Lehmann
Part of the NATO Advanced Study Institutes Series book series (NSSA, volume 40)

Abstract

When growing mammalian cells are damaged by mutagenic treatment DNA replication is disturbed, presumably by the presence of damage in the DNA strands used as templates for replication. In UV-irradiated cells, which have been investigated in great detail, five different phenomena have been observed:-
  1. (1)

    Rapid inhibition of the overall rate of DNA synthesis in each cell, as measured by incorporation of 3H-thymidine. This occurs to a similar extent in nearly all cell types.

     
  2. (2)

    Subsequent recovery of normal rates of DNA synthesis. This recovery occurs at very different rates in different cell types1–3, and is not solely dependent on the capability of the cell type to carry out excision-repair3.

     
  3. (3)

    Reduction in the size of DNA labelled with a pulse of radioactive thymidine shortly after irradiation. This is again very dependent on cell type (e.g. refs. 4–5). It could result from (a) blocking of the progression of the growing forks by damage in the parental DNA, (b) the production of gaps in the daughter strands in the region of the damage (or possibly elsewhere) without the progression of the forks being halted.

     
  4. (4)

    Subsequent increase in size of the initially small DNA labelled soon after irradiation. This implies that the hypothetical blocks are not permanent or that the gaps are sealed.

     
  5. (5)

    Recovery of the ability to synthesize normal-sized DNA as observed by pulse labelling with 3H-thymidine at later times after irradiation.

     

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Copyright information

© Plenum Press, New York 1981

Authors and Affiliations

  • Alan R. Lehmann
    • 1
  1. 1.MRC Cell Mutation UnitUniversity of SussexFalmer, BrightonEngland

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