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

Sriramana Kanginakudru, Marsha DeSmet, Yanique Thomas, Iain M. Morgan, Elliot J. Androphy

Research output: Contribution to journalArticle

13 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)129-136
Number of pages8
JournalVirology
Volume478
DOIs
StatePublished - Apr 1 2015

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Keywords

  • BPV
  • Cell cycle
  • Copy number
  • E2
  • HPV
  • Papillomavirus
  • Replication
  • TopBP1

ASJC Scopus subject areas

  • Virology

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