Graduate Thesis Or Dissertation
 

The kinetics of adenovirus DNA replication

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  • Methods have been developed to measure the time required to complete replication of an adenovirus DNA molecule and the time between rounds of replication of the viral genomes. These methods show that 22 minutes are required to complete replication of an adenovirus DNA molecule at 37° C and that this time is constant throughout infection. The rate limiting step in DNA replication is initiation of a round of replication. The initiation rate decreases over infection and shows saturable kinetics corresponding to a maximum of 50, 000 replication sites per cell. The size of the pool of adenovirus DNA molecules actively replicating is approximately constant over infection, and the DNA molecules in the pool are preferentially replicated. By use of the measured rate parameters based on the strand displacement mechanism of DNA replication (R. L. Lechner and T. J. Kelly, Jr. , 1977. Cell, 12, 1007) several types of experiments were computer simulated to show that this mechanism and measured rate parameters are consistent quantitatively with experimental data. A mechanism is proposed for generation of defective adenovirus DNA inherent in normal replication.
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