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

2017 ◽  
Vol 114 (36) ◽  
pp. 9605-9610 ◽  
Author(s):  
Shuntaro Takahashi ◽  
John A. Brazier ◽  
Naoki Sugimoto

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.

Biochemistry ◽  
2014 ◽  
Vol 53 (32) ◽  
pp. 5315-5322 ◽  
Author(s):  
Connor T. Murphy ◽  
Anisha Gupta ◽  
Bruce A. Armitage ◽  
Patricia L. Opresko

Molecules ◽  
2020 ◽  
Vol 25 (3) ◽  
pp. 705
Author(s):  
Hisae Tateishi-Karimata ◽  
Tatsuya Ohyama ◽  
Takahiro Muraoka ◽  
Shigenori Tanaka ◽  
Kazushi Kinbara ◽  
...  

Methods for stabilizing G-quadruplex formation is a promising therapeutic approach for cancer treatment and other biomedical applications because stable G-quadruplexes efficiently inhibit biological reactions. Oligo and polyethylene glycols are promising biocompatible compounds, and we have shown that linear oligoethylene glycols can stabilize G-quadruplexes. Here, we developed a new modified deoxythymine with dibranched or tribranched tetraethylene glycol (TEG) and incorporated these TEG-modified deoxythymines into a loop region that forms an antiparallel G-quadruplex. We analyzed the stability of the modified G-quadruplexes, and the results showed that the tribranched TEG destabilized G-quadruplexes through entropic contributions, likely through steric hindrance. Interestingly, the dibranched TEG modification increased G-quadruplex stability relative to the unmodified DNA structures due to favorable enthalpic contributions. Molecular dynamics calculations suggested that dibranched TEG interacts with the G-quadruplex through hydrogen bonding and CH-π interactions. Moreover, these branched TEG-modified deoxythymine protected the DNA oligonucleotides from degradation by various nucleases in human serum. By taking advantage of the unique interactions between DNA and branched TEG, advanced DNA materials can be developed that affect the regulation of DNA structure.


FEBS Letters ◽  
1991 ◽  
Vol 281 (1-2) ◽  
pp. 111-113 ◽  
Author(s):  
I.A. Lokhova ◽  
G.A. Nevinsky ◽  
T.S. Godovikova ◽  
E.M. Ivanova ◽  
A.A. Koshkin ◽  
...  

2016 ◽  
Vol 8 (2) ◽  
pp. 275-279 ◽  
Author(s):  
Seyeon Kim ◽  
Jongback Gang

In this study, the G-quadruplex structure was used to detect the enzymatic activity and inhibition of the Klenow fragment exo−(KF−) in the presence ofN-methylmesoporphyrin IX (NMM) which binds specifically to the G-quadruplex.


2021 ◽  
Author(s):  
Anirban Ghosh ◽  
Eric Largy ◽  
Valérie Gabelica

Abstract G-quadruplex DNA structures have become attractive drug targets, and native mass spectrometry can provide detailed characterization of drug binding stoichiometry and affinity, potentially at high throughput. However, the G-quadruplex DNA polymorphism poses problems for interpreting ligand screening assays. In order to establish standardized MS-based screening assays, we studied 28 sequences with documented NMR structures in (usually ∼100 mM) potassium, and report here their circular dichroism (CD), melting temperature (Tm), NMR spectra and electrospray mass spectra in 1 mM KCl/100 mM trimethylammonium acetate. Based on these results, we make a short-list of sequences that adopt the same structure in the MS assay as reported by NMR, and provide recommendations on using them for MS-based assays. We also built an R-based open-source application to build and consult a database, wherein further sequences can be incorporated in the future. The application handles automatically most of the data processing, and allows generating custom figures and reports. The database is included in the g4dbr package (https://github.com/EricLarG4/g4dbr) and can be explored online (https://ericlarg4.github.io/G4_database.html).


2020 ◽  
Vol 53 (1) ◽  
pp. 174-192
Author(s):  
Anurak Thanyacharoen ◽  
Wutiphol Sintunavarat

AbstractIn this article, we prove the generalized Hyers-Ulam stability for the following additive-quartic functional equation:f(x+3y)+f(x-3y)+f(x+2y)+f(x-2y)+22f(x)+24f(y)=13{[}f(x+y)+f(x-y)]+12f(2y),where f maps from an additive group to a complete non-Archimedean normed space.


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