文章基本信息

标题：Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase
本地全文：下载
作者：Shuntaro Takahashi ; John A. Brazier ; John A. Brazier 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2017
卷号：114
期号：36
页码：9605-9610
DOI：10.1073/pnas.1704258114
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Noncanonical DNA structures that stall DNA replication can cause errors in genomic DNA. Here, we investigated how the noncanonical structures formed by sequences in genes associated with a number of diseases impacted DNA polymerization by the Klenow fragment of DNA polymerase. Replication of a DNA sequence forming an i-motif from a telomere, hypoxia-induced transcription factor, and an insulin-linked polymorphic region was effectively inhibited. On the other hand, replication of a mixed-type G-quadruplex (G4) from a telomere was less inhibited than that of the antiparallel type or parallel type. Interestingly, the i-motif was a better inhibitor of replication than were mixed-type G4s or hairpin structures, even though all had similar thermodynamic stabilities. These results indicate that both the stability and topology of structures formed in DNA templates impact the processivity of a DNA polymerase. This suggests that i-motif formation may trigger genomic instability by stalling the replication of DNA, causing intractable diseases.
关键词：replication ; i-motif ; G-quadruplex ; thermodynamics ; molecular crowding