Abstract
The localization and properties of DNA polymerases I and II are reviewed with particular regard to changing activities during rat liver regeneration and in hepatomas. DNA polymerase I is normally found in the nucleus and is also associated with ribosomes, from which it can be eluted and purified. This enzyme does not vary as a function of growth rate or malignancy. DNA polymerase II is normally associated with post-microsomal membrane fragments. During periods of rapid growth its activity rises markedly in both membranes and nuclei. It has been reported from this laboratory that this enzyme exists as a complex together with thymidine kinase, thymidylate synthetase and ribonucleotide reductase. We have speculated that this may be part of a replicative unit for DNA biosynthesis. The selective inhibition of DNA polymerase II by nitrosoureas and their isocyanates is of considerable interest. It is proposed that certain other chemotherapeutic agents may possibly act via a similar type of inhibition of this or other enzymes in this multienzyme complex and that this may also be a fruitful approach in searching for new agents.
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