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Science 11 April 2008:
Vol. 320. no. 5873, pp. 230 - 233
DOI: 10.1126/science.1153201
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Reports

Evidence for Editing of Human Papillomavirus DNA by APOBEC3 in Benign and Precancerous Lesions

Jean-Pierre Vartanian, Denise Guétard, Michel Henry, Simon Wain-Hobson*

Cytidine deaminases of the APOBEC3 family all have specificity for single-stranded DNA, which may become exposed during replication or transcription of double-stranded DNA. Three human APOBEC3A (hA3A), hA3B, and hA3H genes are expressed in keratinocytes and skin, leading us to determine whether genetic editing of human papillomavirus (HPV) DNA occurred. In a study of HPV1a plantar warts and HPV16 precancerous cervical biopsies, hyperedited HPV1a and HPV16 genomes were found. Strictly analogous results were obtained from transfection experiments with HPV plasmid DNA and the three nuclear localized enzymes: hA3A, hA3C, and hA3H. Thus, stochastic or transient overexpression of APOBEC3 genes may expose the genome to a broad spectrum of mutations that could influence the development of tumors.

Molecular Retrovirology Unit, Institut Pasteur, 28 Rue de Docteur Roux, 75724 Paris cedex 15, France.

* To whom correspondence should be addressed. E-mail: simon{at}pasteur.fr

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THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Biochemical Basis of Immunological and Retroviral Responses to DNA-targeted Cytosine Deamination by Activation-induced Cytidine Deaminase and APOBEC3G.
L. Chelico, P. Pham, J. Petruska, and M. F. Goodman (2009)
J. Biol. Chem. 284, 27761-27765
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Defining APOBEC3 Expression Patterns in Human Tissues and Hematopoietic Cell Subsets.
F. A. Koning, E. N. C. Newman, E.-Y. Kim, K. J. Kunstman, S. M. Wolinsky, and M. H. Malim (2009)
J. Virol. 83, 9474-9485
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Expression of Murine APOBEC3 Alleles in Different Mouse Strains and Their Effect on Mouse Mammary Tumor Virus Infection.
C. M. Okeoma, J. Petersen, and S. R. Ross (2009)
J. Virol. 83, 3029-3038
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Stochastic properties of processive cytidine DNA deaminases AID and APOBEC3G.
L. Chelico, P. Pham, and M. F Goodman (2009)
Phil Trans R Soc B 364, 583-593
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APOBEC proteins and intrinsic resistance to HIV-1 infection.
M. H Malim (2009)
Phil Trans R Soc B 364, 675-687
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Powerful mutators lurking in the genome.
V. Petit, J.-P. Vartanian, and S. Wain-Hobson (2009)
Phil Trans R Soc B 364, 705-715
   Abstract »    Full Text »    PDF »
Polymorphisms and Splice Variants Influence the Antiretroviral Activity of Human APOBEC3H.
A. Harari, M. Ooms, L. C. F. Mulder, and V. Simon (2009)
J. Virol. 83, 295-303
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