Trinucleotide repeats affect DNA replication in vivo
Trinucleotide repeats affect DNA replication in vivo
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DOI：
10.1038/ng1197-298
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发表时间：
1997-11-01
期刊：
影响因子：
30.8
通讯作者：
Mirkin, SM
中科院分区：
文献类型：
--
作者：
Samadashwily, GM;Raca, G;Mirkin, SM
（CCG）（n）.（CCG）（n）和（CTG）（n）。将不同长度的CAG（n）重复序列克隆到细菌质粒中，并使用复制中间体的电泳分析跟踪复制叉通过这些重复序列的进展。我们观察到重复DNA内复制叉的停滞，并发现这种效应取决于重复长度、相对于复制起点的重复方向和细胞中蛋白质合成的状态。重复DNA中的中断，类似于在人类基因中观察到的中断，消除了复制障碍。我们的研究结果表明，形成不寻常的DNA结构的三核苷酸重复在滞后链模板可以解释所观察到的复制阻断，并在人类重复扩增相关。
(CCG)(n).(CCG)(n) and (CTG)(n).(CAG)(n) repeats of varying length were cloned into a bacterial plasmid, and the progression of the replication fork through these repeats was followed using electrophoretic analysis of replication intermediates. We observed stalling of the replication fork within repeated DNAs and found that this effect depends on repeat length, repeat orientation relative to the replication origin and the status of protein synthesis in a cell. Interruptions within repeated DNAs, similar to those observed in human genes, abolished the replication blockage. Our results suggest that the formation of unusual DNA structures by trinucleotide repeats in the lagging-strand template may account for the observed replication blockage and have relevance to repeat expansion in humans.