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Genomic instability of the host cell induced by the human papillomavirus replication machinery
Author(s) -
Kadaja Meelis,
Sumerina Alina,
Verst Tatjana,
Ojarand Mari,
Ustav Ene,
Ustav Mart
Publication year - 2007
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601665
Subject(s) - biology , genome instability , human papillomavirus , genetics , replication (statistics) , virology , computational biology , dna , dna damage , medicine
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.