Correlated target search by uracil-DNA glycosylase in the presence of bulky adducts and DNA-binding ligands
- Authors: Mechetin G.V.1, Dyatlova E.A.1, Sinyakov A.N.1, Ryabinin V.A.1, Vorobjev P.E.1,2, Zharkov D.O.1,2
-
Affiliations:
- Institute of Chemical Biology and Fundamental Medicine
- Novosibirsk State University
- Issue: Vol 43, No 1 (2017)
- Pages: 23-28
- Section: Article
- URL: https://journals.rcsi.science/1068-1620/article/view/228375
- DOI: https://doi.org/10.1134/S106816201606008X
- ID: 228375
Cite item
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.
About the authors
G. V. Mechetin
Institute of Chemical Biology and Fundamental Medicine
Email: dzharkov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
E. A. Dyatlova
Institute of Chemical Biology and Fundamental Medicine
Email: dzharkov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
A. N. Sinyakov
Institute of Chemical Biology and Fundamental Medicine
Email: dzharkov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
V. A. Ryabinin
Institute of Chemical Biology and Fundamental Medicine
Email: dzharkov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090
P. E. Vorobjev
Institute of Chemical Biology and Fundamental Medicine; Novosibirsk State University
Email: dzharkov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk, 630090
D. O. Zharkov
Institute of Chemical Biology and Fundamental Medicine; Novosibirsk State University
Author for correspondence.
Email: dzharkov@niboch.nsc.ru
Russian Federation, Novosibirsk, 630090; Novosibirsk, 630090