Large T antigen binds to specific sites within the Ori to promote replication of the viral genome. Binding first unwinds the DNA. Then T antigen associates with replication protein A followed by DNA polymerase a primase to form an initiation complex. Association with primase is species specific. As a result, SV40 productively infects only monkey cells and mouse polyomavirus only mouse cells. After initiation by primase, DNA polymerase takes over and replication proceeds. DNA synthesis is bidirectional and when the replication forks meet about halfway round the molecule, the daughter genomes separate, aided by topoisomerase II (Fig. 1.7A).
Large T antigen also regulates the transcription of late mRNAs, which are transcribed from the opposite strand as the early mRNAs (Fig. 6.23). Differential splicing leads to
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