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

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 repli...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology (New York) 2018-11, Vol.52 (6), p.922-928
Main Authors: Dyrkheeva, N. S., Lebedeva, N. A., Sherstyuk, Yu. V., Abramova, T. V., Silnikov, V. N., Lavrik, O. I.
Format: Article
Language:English
Subjects:
Antiviral agents
Biochemistry
Biomedical and Life Sciences
Cytosine
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA damage
DNA polymerase
DNA repair
DNA-directed DNA polymerase
Endonuclease
HIV
Human Genetics
Human immunodeficiency virus
Insertion
Life Sciences
Nucleosides
Nucleotides
Phosphodiesterase
Primers
Proofreading
Ribonucleic acid
Ribose
RNA
RNA-directed DNA polymerase
Structural-Functional Analysis of Biopolymers and Their Complexes
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0026-8933
1608-3245
DOI:10.1134/S0026893318060067