Homologous recombination repair factors Rad51 and BRCA1 are necessary for productive replication of human papillomavirus 31

William H. Chappell, Dipendra Gautam, Suzan T. Ok, Bryan A. Johnson, Daniel C. Anacker, Cary A. Moody

Research output: Contribution to journalArticlepeer-review

66 Scopus citations


High-risk human papillomavirus 31 (HPV31)-positive cells exhibit constitutive activation of the ATM-dependent DNA damage response (DDR), which is necessary for productive viral replication. In response to DNA double-strand breaks (DSBs), ATM activation leads to DNA repair through homologous recombination (HR), which requires the principal recombinase protein Rad51, as well as BRCA1. Previous studies from our lab demonstrated that Rad51 and BRCA1 are expressed at high levels in HPV31-positive cells and localize to sites of viral replication. These results suggest that HPV may utilize ATM activity to increase HR activity as a means to facilitate viral replication. In this study, we demonstrate that high-risk HPV E7 expression alone is sufficient for the increase in Rad51 and BRCA1 protein levels. We have found that this increase occurs, at least in part, at the level of transcription. Studies analyzing protein stability indicate that HPV may also protect Rad51 and BRCA1 from turnover, contributing to the overall increase in cellular levels. We also demonstrate that Rad51 is bound to HPV31 genomes, with binding increasing per viral genome upon productive replication. We have found that depletion of Rad51 and BRCA1, as well as inhibition of Rad51's recombinase activity, abrogates productive viral replication upon differentiation. Overall, these results indicate that Rad51 and BRCA1 are required for the process of HPV31 genome amplification and suggest that productive replication occurs in a manner dependent upon recombination.

Original languageEnglish (US)
Pages (from-to)2639-2652
Number of pages14
JournalJournal of virology
Issue number5
StatePublished - 2016
Externally publishedYes

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology


Dive into the research topics of 'Homologous recombination repair factors Rad51 and BRCA1 are necessary for productive replication of human papillomavirus 31'. Together they form a unique fingerprint.

Cite this