Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions
Evidence for editing of human papillomavirus DNA by APOBEC3 in benign and precancerous lesions
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DOI：
10.1126/science.1153201
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发表时间：
2008-04-11
期刊：
影响因子：
56.9
通讯作者：
Wain-Hobson, Simon
中科院分区：
文献类型：
--
作者：
Vartanian, Jean-Pierre;Guetard, Denise;Wain-Hobson, Simon
APOBEC3 家族的胞苷脱氨酶均对单链 DNA 具有特异性，在双链 DNA 复制或转录过程中可能会暴露出来。三种人类 APOBEC3A (hA3A)、hA3B 和 hA3H 基因在角质形成细胞和皮肤中表达，使我们能够确定是否发生了人乳头瘤病毒 (HPV) DNA 的基因编辑。在一项针对 HPV1a 跖疣和 HPV16 癌前宫颈活检的研究中，发现了过度编辑的 HPV1a 和 HPV16 基因组。用 HPV 质粒 DNA 和三种核定位酶：hA3A、hA3C 和 hA3H 进行转染实验，获得了严格类似的结果。因此，APOBEC3 基因的随机或短暂过度表达可能会使基因组暴露于可能影响肿瘤发展的广泛突变。
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.