Samadashwily G M, Raca G, Mirkin S M
Department of Molecular Genetics, University of Illinois at Chicago 60607, USA.
Nat Genet. 1997 Nov;17(3):298-304. doi: 10.1038/ng1197-298.
(CGG)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.
将不同长度的（CGG）n.（CCG）n和（CTG）n.（CAG）n重复序列克隆到细菌质粒中，并通过对复制中间体进行电泳分析来追踪复制叉通过这些重复序列的进程。我们观察到复制叉在重复DNA内停滞，并发现这种效应取决于重复序列的长度、相对于复制起点的重复序列方向以及细胞中蛋白质合成的状态。重复DNA内的中断，类似于在人类基因中观察到的情况，消除了复制阻滞。我们的结果表明，滞后链模板中的三核苷酸重复序列形成异常DNA结构可能是观察到的复制阻滞的原因，并且与人类中的重复序列扩增有关。
