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Correlated target search by uracil-DNA glycosylase in the presence of bulky adducts and DNA-binding ligands

Abstract

Many proteins specific for rare targets in DNA, such as transcription factors, restriction endonucleases, and DNA repair enzymes, search for their targets by one-dimensional diffusion along DNA. One of these proteins is uracil-DNA glycosylase (Ung), which excises the uracil bases formed by rare events of cytosine deamination. We have studied the ability of Ung to move along DNA with its path hindered by bulky DNA covalent adducts (fluorescein) or ligands blocking the major or minor DNA groove. The fluorescein adduct strongly inhibits translocation only along double-stranded DNA, whereas noncovalently bound ligands partly inhibit DNA cleavage but barely affect translocation. The ability of uracil-DNA glycosylase to search for its targets in the presence of molecules competing for DNA binding may be important for DNA repair in the intracellular environment.

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Abbreviations

Acr:

(6-chloro-2-methoxyacridin-9-yl)propane-1,3-diamine

T-FAM:

fluorescein-containing thymine

Ung:

uracil-DNA-N-glycosylase

ODN:

oligodeoxyribonucleotide

BER:

base excision repair

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Correspondence to D. O. Zharkov.

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Original Russian Text © G.V. Mechetin, E.A. Dyatlova, A.N. Sinyakov, V.A. Ryabinin, P.E. Vorobjev, D.O. Zharkov, 2017, published in Bioorganicheskaya Khimiya, 2017, Vol. 43, No. 1, pp. 29–34.

The paper is based on the materials of the “Chemical Biology 2016” conference; Novosibirsk, Russia, July 24–29, 2016.

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Mechetin, G.V., Dyatlova, E.A., Sinyakov, A.N. et al. Correlated target search by uracil-DNA glycosylase in the presence of bulky adducts and DNA-binding ligands. Russ J Bioorg Chem 43, 23–28 (2017). https://doi.org/10.1134/S106816201606008X

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  • DOI: https://doi.org/10.1134/S106816201606008X

Keywords

  • uracil-DNA glycosylase
  • DNA target search
  • covalent DNA adducts
  • minor groove binders
  • triplex-forming oligonucleotides