Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase

Takahashi, S., Brazier, J. A. ORCID: https://orcid.org/0000-0002-4952-584X and Sugimoto, N. (2017) Topological impact of noncanonical DNA structures on Klenow fragment of DNA polymerase. Proceedings of the National Academy of Sciences of the United States of America, 114 (36). pp. 9605-9610. ISSN 0027-8424 doi: 10.1073/pnas.1704258114

Abstract/Summary

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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/73123
Identification Number/DOI	10.1073/pnas.1704258114
Refereed	Yes
Divisions	Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Medicinal Chemistry Research Group
Publisher	National Academy of Sciences
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