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Title: Levels of the E2 interacting protein TopBP1 modulate papillomavirus maintenance stage replication

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. - Highlights: • Protein interaction study confirmed In-situ interaction between TopBP1 and E2. • TopBP1 present at papillomavirus ori in G1/S and early S phase of cell cycle. • TopBP1 knockdown increased, over-expression reduced virus replication. • TopBP1 protein level change did not influence cell survival or cell cycle. • TopBP1 displaced from papillomavirus ori after initiation of replication.
Authors:
 [1] ;  [1] ;  [2] ;  [3] ;  [1] ;  [4]
  1. Department of Dermatology, Indiana University School of Medicine, Indianapolis, IN (United States)
  2. Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN (United States)
  3. VCU Philips Institute for Oral Health Research, Virginia Commonwealth University, Richmond, Virginia (United States)
  4. (United States)
Publication Date:
OSTI Identifier:
22470162
Resource Type:
Journal Article
Resource Relation:
Journal Name: Virology; Journal Volume: 478; Other Information: Copyright (c) 2015 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CELL CYCLE; DNA; DNA DAMAGES; DNA REPLICATION; HUMAN POPULATIONS; INTERACTIONS; PROTEINS; VIRUSES