title: Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication.
abstract: The 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.
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: skangina@iu.edu.
authors: Sriramana
authors: S
authors: Kanginakudru
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: mdesmet@iupui.edu.
authors: Marsha
authors: M
authors: DeSmet
authors: Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: ysthomas@umail.iu.edu.
authors: Yanique
authors: Y
authors: Thomas
authors: VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia, USA. Electronic address: immorgan@vcu.edu.
authors: Iain M
authors: IM
authors: Morgan
authors: Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN, USA; Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA. Electronic address: eandro@iu.edu.
authors: Elliot J
authors: EJ
authors: Androphy
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D006801:Humans; D051379:Mice; D009856:Oncogene Proteins, Viral / Q000378:metabolism*; D027383:Papillomaviridae / Q000502:physiology*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; C051550:E2 protein, Bovine papillomavirus; C054855:E2 protein, Human papillomavirus type 16; C098597:E2 protein, Human papillomavirus type 31; D009856:Oncogene Proteins, Viral; C492846:Topbp1 protein, mouse; D014764:Viral Proteins
keywords: BPV; Cell cycle; Copy number; E2; HPV; Papillomavirus; Replication; TopBP1