Kanginakudru, SriramanaDeSmet, MarshaThomas, YaniqueMorgan, Iain M.Androphy, Elliot J.2016-08-052016-08-052015-04Kanginakudru, S., DeSmet, M., Thomas, Y., Morgan, I. M., & Androphy, E. J. (2015). Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication. Virology, 478, 135–142. http://doi.org/10.1016/j.virol.2015.01.0111096-0341https://hdl.handle.net/1805/10583The evolutionarily conserved DNA topoisomerase II beta-binding protein 1 (TopBP1) functions in DNA replication, DNA damage response, and cell survival. We analyzed the role of TopBP1 in human and bovine papillomavirus genome replication. Consistent with prior reports, TopBP1 co-localized in discrete nuclear foci and was in complex with papillomavirus E2 protein. Similar to E2, TopBP1 is recruited to the region of the viral origin of replication during G1/S and early S phase. TopBP1 knockdown increased, while over-expression decreased transient virus replication, without affecting cell cycle. Similarly, using cell lines harboring HPV-16 or HPV-31 genome, TopBP1 knockdown increased while over-expression reduced viral copy number relative to genomic DNA. We propose a model in which TopBP1 serves dual roles in viral replication: it is essential for initiation of replication yet it restricts viral copy number.en-USPublisher PolicyCarrier ProteinsmetabolismDNA-Binding ProteinsHost-Pathogen InteractionsOncogene Proteins, ViralPapillomaviridaephysiologyViral ProteinsVirus ReplicationArticle