Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions.
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.
Vartanian
Jean-Pierre
JP
Molecular Retrovirology Unit, Institut Pasteur, 28 Rue de Docteur Roux, 75724 Paris cedex 15, France.
Guétard
Denise
D
Henry
Michel
M
Wain-Hobson
Simon
S
D000071478:APOBEC Deaminases; D002460:Cell Line; D002584:Cervix Uteri / Q000821:virology; D003562:Cytidine / Q000378:metabolism; D003564:Cytidine Deaminase; D043525:Cytosine Deaminase / Q000378:metabolism*; D053843:DNA Mismatch Repair; D004279:DNA, Viral / Q000235:genetics / Q000378:metabolism*; D005260:Female; D016679:Genome, Viral; D052162:Human papillomavirus 16 / Q000235:genetics*; D006801:Humans; D052692:Mupapillomavirus / Q000235:genetics*; D009154:Mutation; D030361:Papillomavirus Infections / Q000201:enzymology / Q000821:virology; D011230:Precancerous Conditions / Q000201:enzymology / Q000821:virology*; D014162:Transfection; D002583:Uterine Cervical Neoplasms / Q000201:enzymology / Q000821:virology*; D014860:Warts / Q000201:enzymology / Q000821:virology*
D004279:DNA, Viral; D003562:Cytidine; D043525:Cytosine Deaminase; D000071478:APOBEC Deaminases; C502889:APOBEC3 proteins, human; D003564:Cytidine Deaminase