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Article

  • The EMBO Journal (2007) 26, 2180 - 2191
  • doi:10.1038/sj.emboj.7601665

Published online: 29 March 2007

Genomic instability of the host cell induced by the human papillomavirus replication machinery

Meelis Kadaja1, Alina Sumerina1, Tatjana Verst1, Mari Ojarand1, Ene Ustav2 and Mart Ustav1,2

  1. Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia
  2. Institute of Technology, University of Tartu, Tartu, Estonia

Correspondence to:

Mart Ustav, Department of Biomedical Technology, Institute of Technology, University of Tartu and Estonian Biocentre, Nooruse 1, Tartu 50411, Estonia. Tel.: +372 737 4800; Fax: +372 737 4900; E-mail: mart.ustav@ut.ee

Received 27 September 2006; Accepted 5 March 2007

Development of invasive cervical cancer upon infection by 'high-risk' human papillomavirus (HPV) in humans is a stepwise process in which some of the initially episomal 'high-risk' type of HPVs (HR-HPVs) integrate randomly into the host cell genome. We show that HPV replication proteins E1 and E2 are capable of inducing overamplification of the genomic locus where HPV origin has been integrated. Clonal analysis of the cells in which the replication from integrated HPV origin was induced showed excision, rearrangement and de novo integration of the HPV containing and flanking cellular sequences. These data suggest that papillomavirus replication machinery is capable of inducing genomic changes of the host cell that may facilitate the formation of the HPV-dependent cancer cell.

  • Keywords:

    • cancer,
    • DNA replication,
    • genomic instability,
    • HPV,
    • papillomavirus