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含恶唑酮碱基对的稳定性对DNA延伸的影响。

Effects of stability of base pairs containing an oxazolone on DNA elongation.

作者信息

Suzuki Masayo, Ohtsuki Kazuya, Kino Katsuhito, Kobayashi Teruhiko, Morikawa Masayuki, Kobayashi Takanobu, Miyazawa Hiroshi

机构信息

Kagawa School of Pharmaceutical Sciences, Tokushima Bunri University, 1314-1 Shido, Sanuki, Kagawa 769-2193, Japan.

出版信息

J Nucleic Acids. 2014;2014:178350. doi: 10.1155/2014/178350. Epub 2014 Dec 7.

DOI:10.1155/2014/178350
PMID:25574383
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4273591/
Abstract

The nucleoside 2,2,4-triamino-5(2H)-oxazolone (Oz) can result from oxidative damage to guanine residues in DNA. Despite differences among the three polymerases (Pol β, KF exo(-), and Pol η) regarding nucleotide incorporation patterns opposite Oz, all three polymerases can incorporate guanine opposite Oz. Based on ab initio calculations, we proposed a structure for a stable Oz:G base pair. Here, to assess the stability of each Oz-containing base pair (Oz:G, Oz:A, Oz:C, and Oz:T) upon DNA replication, we determined the efficiency of Pol β-, KF exo(-)-, or Pol η-catalyzed primer extension beyond each base pair. With each polymerase, extension beyond Oz:G was more efficient than that beyond Oz:A, Oz:C, or Oz:T. Moreover, thermal denaturation studies revealed that the T m value for the duplex containing Oz:G was significantly higher than those obtained for duplexes containing Oz:A, Oz:C, or Oz:T. Therefore, the results from ab initio calculations along with those from DNA replication assays and thermal denaturation experiments supported the conclusion that Oz:G is the most stable of the Oz-containing base pairs.

摘要

核苷2,2,4-三氨基-5(2H)-恶唑酮(Oz)可由DNA中鸟嘌呤残基的氧化损伤产生。尽管三种聚合酶(Pol β、KF exo(-)和Pol η)在与Oz相对的核苷酸掺入模式上存在差异,但这三种聚合酶都能在Oz相对位置掺入鸟嘌呤。基于从头算计算,我们提出了一种稳定的Oz:G碱基对结构。在此,为了评估每个含Oz碱基对(Oz:G、Oz:A、Oz:C和Oz:T)在DNA复制时的稳定性,我们测定了Pol β、KF exo(-)或Pol η催化的引物延伸越过每个碱基对的效率。对于每种聚合酶,越过Oz:G的延伸比越过Oz:A、Oz:C或Oz:T的延伸更有效。此外,热变性研究表明,含Oz:G的双链体的熔解温度(Tm)值显著高于含Oz:A、Oz:C或Oz:T的双链体的Tm值。因此,从头算计算结果以及DNA复制测定和热变性实验结果支持了Oz:G是含Oz碱基对中最稳定的这一结论。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/0331ec1cd58b/JNA2014-178350.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/d00df3e8a51c/JNA2014-178350.sch.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/382c3c8d6662/JNA2014-178350.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/4307b405ea28/JNA2014-178350.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/66dd78378a3d/JNA2014-178350.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/86074708bab0/JNA2014-178350.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/4b8ff0a26439/JNA2014-178350.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/0331ec1cd58b/JNA2014-178350.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/d00df3e8a51c/JNA2014-178350.sch.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/382c3c8d6662/JNA2014-178350.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/4307b405ea28/JNA2014-178350.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/66dd78378a3d/JNA2014-178350.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/86074708bab0/JNA2014-178350.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/4b8ff0a26439/JNA2014-178350.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e7a/4273591/0331ec1cd58b/JNA2014-178350.006.jpg

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