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. Lavrik

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)922-928
Number of pages7
JournalMolecular Biology
Volume52
Issue number6
DOIs
Publication statusPublished - 1 Nov 2018

Keywords

  • HIV reverse transcriptase
  • morpholino nucleoside triphosphates
  • proofreading of DNA synthesis
  • TDP1
  • АРЕ1
  • 1
  • NUCLEOSIDE
  • REPAIR
  • REVERSE-TRANSCRIPTASE
  • POLYMERASE-BETA

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