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Publisher Summary This chapter states that physiological experiments demonstrating variations of DNA polymerase activities were first done in mammalian systems, whereas the first relevant genetic experiments in bacteria came 12 years after the discovery of Escherichia coli DNA polymerase I. Mammalian DNA polymerase can be isolated and purified without the major problems that arise from associated nucleases. For this reason, it is relatively simple to do mechanistic studies with these enzymes. With bacterial enzymes, on the other hand, there are logical difficulties in proving the nature of the template initiator system required. Purification of mammalian DNA polymerases to homogeneity has been somewhat of a problem, and the first such homogeneous DNA polymerase, the low-molecular-weight DNA polymerase from calf thymus chromatin, is also described in the chapter. The chapter discusses the nature of template initiator systems, the major DNA polymerase activities in cell fractions and the properties of purified mammalian enzymes. Future direction will start with the information presented and eventually proceed into the more complex “replication systems” including the “associated proteins” clearly required for DNA replication. To analyze the participation of the known DNA polymerases in DNA replication, polymerase mutants and selective inhibitors are sorely needed. |
