Breakpoints of gross deletions coincide with non-B DNA conformations
Breakpoints of gross deletions coincide with non-B DNA conformations
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DOI：
10.1073/pnas.0405974101
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发表时间：
2004-09-28
影响因子：
11.1
通讯作者：
Wells, RD
中科院分区：
文献类型：
--
作者：
Bacolla, A;Jaworski, A;Wells, RD
基因组重排是一种常见的不稳定性来源，但涉及的机制知之甚少。来自人类PKD 1基因的2.5 kbp聚（嘌呤-嘧啶）序列，已知形成非B DNA结构，诱导质粒中的长缺失和其他不稳定性，这些不稳定性由错配修复介导，在某些情况下，转录。断裂点发生在预测的非B DNA结构。距离测量还表明，一个显着的接近交替嘌呤-嘧啶和寡（嘌呤-嘧啶）道断点交界处222粗删除和易位，分别涉及人类疾病。在分析的11个缺失中，断裂点可由非B DNA结构形成来解释。我们的结论是，替代DNA构象通过重组修复活动触发基因组重排。
Genomic rearrangements are a frequent source of instability, but the mechanisms involved are poorly understood. A 2.5-kbp poly(purine-pyrimidine) sequence from the human PKD1 gene, known to form non-B DNA structures, induced long deletions and other instabilities in plasmids that were mediated by mismatch repair and, in some cases, transcription. The breakpoints occurred at predicted non-B DNA structures. Distance measurements also indicated a significant proximity of alternating purine-pyrimidine and oligo(purine-pyrimidine) tracts to breakpoint junctions in 222 gross deletions and translocations, respectively, involved in human diseases. In 11 deletions analyzed, breakpoints were explicable by non-B DNA structure formation. We conclude that alternative DNA conformations trigger genomic rearrangements through recombination-repair activities.