University of Massachusetts Medical School Faculty Publications

UMMS Affiliation

Department of Medicine, Division of Infectious Diseases and Immunology

Publication Date

2013-1

Document Type

Article

Subjects

Cell Cycle Proteins; Cells, Cultured; *DNA Damage; *DNA Replication; Female; Gene Expression; Genomic Instability; Human papillomavirus 16; Humans; Papillomavirus E7 Proteins; *Polyploidy; Up-Regulation

Disciplines

Cancer Biology | Genetic Phenomena | Molecular Genetics | Virology | Virus Diseases

Abstract

Human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis. Genomic instability caused by HPV allows cells to acquire additional mutations required for malignant transformation. Genomic instability in the form of polyploidy has been demonstrated to play an important role in cervical carcinogenesis. We have recently found that HPV-16 E7 oncogene induces polyploidy in response to DNA damage; however, the mechanism is not known. Here we present evidence demonstrating that HPV-16 E7-expressing cells have an intact G(2) checkpoint. Upon DNA damage, HPV-16 E7-expressing cells arrest at the G(2) checkpoint and then undergo rereplication, a process of successive rounds of host DNA replication without entering mitosis. Interestingly, the DNA replication initiation factor Cdt1, whose uncontrolled expression induces rereplication in human cancer cells, is upregulated in E7-expressing cells. Moreover, downregulation of Cdt1 impairs the ability of E7 to induce rereplication. These results demonstrate an important role for Cdt1 in HPV E7-induced rereplication and shed light on mechanisms by which HPV induces genomic instability.

Rights and Permissions

Publisher PDF posted as allowed by the publisher's author rights policy at http://journals.asm.org/site/misc/ASM_Author_Statement.xhtml.

DOI of Published Version

10.1128/JVI.02038-12

Source

J Virol. 2013 Jan;87(2):1200-10. doi: 10.1128/JVI.02038-12. Epub 2012 Nov 14. Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Journal of virology

PubMed ID

23152514

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