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Molecular Biology

, Volume 52, Issue 6, pp 922–928 | Cite as

Excision of Carbohydrate-Modified dNMP Analogues from DNA 3' end by Human Apurinic/Apyrimidinic Endonuclease 1 (APE1) and Tyrosyl-DNA Phosphodiesterase 1 (TDP1)

  • N. S. Dyrkheeva
  • N. A. Lebedeva
  • Yu. V. Sherstyuk
  • T. V. Abramova
  • V. N. Silnikov
  • O. I. LavrikEmail author
STRUCTURAL-FUNCTIONAL ANALYSIS OF BIOPOLYMERS AND THEIR COMPLEXES
  • 51 Downloads

Abstract

We have studied the excision efficiency of human apurinic/apyrimidinic endonuclease 1 (APE1) and tyrosyl-DNA phosphodiesterase 1 (TDP1) on matched or mismatched bases located at the 3' end of DNA primers. We have used model DNA duplexes, which mimic DNA structures that occur during either replication (DNA with a 3' recessed end) or repair (DNA with a single-strand break). Both APE1 and TDP1 are more efficient in removing ribose-modified dNMP residues from mismatched pairs rather than canonical pairs. Thus, both of these enzymes may act as proofreading factors during the repair synthesis catalyzed by DNA polymerases including DNA polymerase β (Polβ). The design of new DNA polymerase inhibitors, which act as DNA or RNA chain terminators, is one of the main strategies in the development of antiviral agents. The excision efficacy of APE1 and TDP1 has also been studied for 3'-modified DNA duplexes that contain ddNMP or phosphorylated morpholino nucleosides (MorB) commonly used as terminators in the DNA synthesis. We have also investigated the insertion of ddNTP and morpholino nucleotides catalyzed by Polβ and human immunodeficiency virus reverse transcriptase. This experiment has pointed to MorCyt, cytosine-containing morpholino nucleoside, as a potential antiviral agent.

Keywords:

proofreading of DNA synthesis morpholino nucleoside triphosphates АРЕ1 TDP1 HIV reverse transcriptase 

Notes

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Copyright information

© Pleiades Publishing, Inc. 2018

Authors and Affiliations

  • N. S. Dyrkheeva
    • 1
  • N. A. Lebedeva
    • 1
  • Yu. V. Sherstyuk
    • 1
  • T. V. Abramova
    • 1
  • V. N. Silnikov
    • 1
  • O. I. Lavrik
    • 1
    • 2
    • 3
    Email author
  1. 1.Institute of Chemical Biology and Fundamental Medicine, Siberian Branch, Russian Academy of SciencesNovosibirskRussia
  2. 2.Novosibirsk State UniversityNovosibirskRussia
  3. 3.Altai State UniversityBarnaulRussia

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