Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 114, Issue 36, Pages 9605-9610Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1704258114
Keywords
replication; i-motif; G-quadruplex; thermodynamics; molecular crowding
Categories
Funding
- Ministry of Education, Culture, Sports, Science and Technology (MEXT)
- Japan Society for the Promotion of Science (JSPS) [JP17H06351]
- MEXT-Supported Program for the Strategic Research Foundation at Private Universities, Japan
- Hirao Taro Foundation of Konan Gakuen for Academic Research
- Okazaki Kazuo Foundation of Konan Gakuen for Advanced Scientific Research
- Chubei Itoh Foundation
- Hyogo Science and Technology Association
- Grants-in-Aid for Scientific Research [17H06351, 16H02283, 17K01968, 16K14041] Funding Source: KAKEN
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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.
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