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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases,a pathway for DNA catabolism
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Somatic hypermutation of human mitochondrial and nuclear DNA by APOBEC3 cytidine deaminases,a pathway for DNA catabolism

机译：APOBEC3胞嘧啶脱氨酶对人线粒体和核DNA的体细胞超突变，DNA分解代谢的途径

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摘要

The human APOBEC3 (A3A-A3H) locus encodes six cytidine deaminases that edit single-stranded DNA, the result being DNA peppered with uridine. Although several cytidine deaminases are clearly restriction factors for retroviruses and hepadnaviruses, it is not known if APOBEC3 enzymes have roles outside of these settings. It is shown here that both human mitochondrial and nuclear DNA are vulnerable to somatic hypermutation by A3 deaminases, with APOBEC3A standing out among them. The degree of editing is much greater in patients lacking the uracil DNA-glycolyase gene, indicating that the observed levels of editing reflect a dynamic composed of A3 editing and DNA catabolism involving uracil DNA-glycolyase. Nonetheless, hyper- and lightly mutated sequences went hand in hand, raising the hypothesis that recurrent low-level mutation by APOBEC3A could catalyze the transition from a healthy to a cancer genome.
机译：人APOBEC3（A3A-A3H）基因座编码6个胞嘧啶脱氨酶，这些胞嘧啶脱氨酶可编辑单链DNA，其结果是尿苷添加了DNA。尽管几种胞嘧啶脱氨酶显然是逆转录病毒和肝炎病毒的限制因子，但不知道APOBEC3酶是否在这些环境之外起作用。此处显示，人类线粒体和核DNA都容易受到A3脱氨酶的体细胞超突变作用，其中APOBEC3A脱颖而出。缺乏尿嘧啶DNA-糖酵解酶基因的患者的编辑程度要高得多，这表明观察到的编辑水平反映了由A3编辑和涉及尿嘧啶DNA-糖酵解酶的DNA分解代谢组成的动态变化。但是，高突变和轻突变序列是并驾齐驱的，这提出了APOBEC3A反复发生的低水平突变可以催化从健康基因组向癌症基因组转变的假设。

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    Rodolphe Suspene; Marie-Ming Aynaud; Denise Guetard; Michel Henry; Grace Eckhoff; Agnes Marchio; Pascal Pineau; Anne Dejean; Jean-Pierre Vartanian; Simon Wain-Hobson;

  • 作者单位

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

    Nuclear Organization and Oncogenesis Unit,75724 Paris cedex 15, France;

    Nuclear Organization and Oncogenesis Unit,75724 Paris cedex 15, France;

    Nuclear Organization and Oncogenesis Unit,75724 Paris cedex 15, France,lnstitut National de la Sante et de la Recherche Medicale, U579, 75724 Paris cedex 15, France;

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

    lnstitut Pasteur, Molecular Retrovirology Unit, Centre National de la Recherche Scientifique URA3015;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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