Non-B DNA conformations, mutagenesis and disease.
Non-B DNA conformations, mutagenesis and disease.
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DOI：
10.1016/j.tibs.2007.04.003
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发表时间：
2007-06
影响因子：
13.8
通讯作者：
R. Wells
中科院分区：
文献类型：
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作者：
R. Wells
最近的发现表明，已知采用非B DNA构象（如三链体、十字形、滑动结构、左手Z-DNA和四链体）的简单重复DNA序列具有致突变性。这种突变是由于非B DNA构象而不是由于DNA测序仪中的传统右手沃森-克里克B型。这些非B结构的人类遗传后果是1020种神经系统疾病，1050种基因组疾病（由严重缺失，倒位，复制和易位引起），以及几种涉及简单重复序列多态性的精神疾病。因此，生物化学，遗传学和基因组学研究的融合已经证明了一种新的范式，涉及非B DNA构象作为诱变特异性决定因素，而不是序列本身。
Recent discoveries have revealed that simple repeating DNA sequences, which are known to adopt non-B DNA conformations (such as triplexes, cruciforms, slipped structures, left-handed Z-DNA and tetraplexes), are mutagenic. The mutagenesis is due to the non-B DNA conformation rather than to the DNA sequenceper sein the orthodox right-handed Watson-Crick B-form. The human genetic consequences of these non-B structures are ∼20 neurological diseases, ∼50 genomic disorders (caused by gross deletions, inversions, duplications and translocations), and several psychiatric diseases involving polymorphisms in simple repeating sequences. Thus, the convergence of biochemical, genetic and genomic studies has demonstrated a new paradigm implicating the non-B DNA conformations as the mutagenesis specificity determinants, not the sequences as such.