Translesion DNA replication proteins as molecular targets for cancer prevention.
Translesion DNA replication proteins as molecular targets for cancer prevention.
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DOI：
10.1016/j.canlet.2005.10.013
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发表时间：
2006-09
期刊：
影响因子：
9.7
通讯作者：
N. B. Watson;S. Mukhopadhyay;W. Mcgregor
中科院分区：
文献类型：
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作者：
N. B. Watson;S. Mukhopadhyay;W. Mcgregor
DNA突变通常被认为在癌症的发展中具有病因学作用。如果是这样，那么减少这种突变的频率将减少由诱变剂引起的癌症的发病率。在阐明致癌物质诱导突变的分子机制方面的最新进展表明，含有复制阻断加合物的DNA模板的复制是通过容易出错的DNA聚合酶完成的。这些聚合酶有宽松的碱基配对要求，并且可以插入碱基穿过内合模板，但有潜在的致突变后果。原则上，这些蛋白质提供了新的和有吸引力的分子靶标，以减少诱变。如果这可以在体内完成而不增加对致癌物的细胞毒性反应，那么可以设计新的化学预防策略，以在疾病症状出现之前降低暴露人群的癌症风险。
Mutations in DNA are generally considered to have an etiologic role in the development of cancer. If so, it follows that reducing the frequency of such mutations will reduce the incidence of cancer induced by mutagens. Recent advances in elucidating the molecular mechanisms of carcinogen-induced mutagenesis indicate that replication of DNA templates that contain replication-blocking adducts is accomplished with error-prone DNA polymerases. These polymerases have relaxed base-pairing requirements, and can insert bases across from adducted templates, but with potentially mutagenic consequences. In principle, these proteins present new and attractive molecular targets to reduce mutagenesis. If this can be done in vivo without increasing cytotoxic responses to carcinogens, then novel chemopreventive strategies can be designed to reduce the risk of cancer in exposed populations prior to the appearance of disease symptoms.