Interaction of the papillomavirus E2 protein with mitotic chromosomes

The bovine papillomavirus E2 transactivator protein is a multifunctional pr otein that activates viral transcription, cooperates in initiation of viral DNA replication, and is required for long-term episomal maintenance of vir al genomes. We have shown previously that the E2 transactivator protein and bovine papillomavirus type 1 genomes are associated with mitotic chromosom es and have proposed that E2 links the genomes to cellular chromosomes to e nsure segregation to daughter nuclei. In this study, we show that E2 is ass ociated with cellular chromosomes at all stages of mitosis. We also further map the regions of E2 that are required for this association. The transact ivation domain of E2 is necessary and sufficient to mediate the interaction with mitotic chromosomes; the DNA binding domain, and the flexible hinge r egion that separates the two domains, is not required. Furthermore, mutatio n of previously identified phosphorylation sites (serine residues 235, 298, and 301) has no effect on the ability of the E2 protein to bind mitotic ch romosomes. (C) 2000 Academic Press.