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Effective Distance for DNA-Mediated Charge Transport between Repair Proteins

[Image: see text] The stacked aromatic base pairs within the DNA double helix facilitate charge transport down its length in the absence of lesions, mismatches, and other stacking perturbations. DNA repair proteins containing [4Fe4S] clusters can take advantage of DNA charge transport (CT) chemistry...

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Autores principales: Tse, Edmund C. M., Zwang, Theodore J., Bedoya, Sebastian, Barton, Jacqueline K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Chemical Society 2019
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346725/
https://www.ncbi.nlm.nih.gov/pubmed/30693326
http://dx.doi.org/10.1021/acscentsci.8b00566
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author Tse, Edmund C. M.
Zwang, Theodore J.
Bedoya, Sebastian
Barton, Jacqueline K.
author_facet Tse, Edmund C. M.
Zwang, Theodore J.
Bedoya, Sebastian
Barton, Jacqueline K.
author_sort Tse, Edmund C. M.
collection PubMed
description [Image: see text] The stacked aromatic base pairs within the DNA double helix facilitate charge transport down its length in the absence of lesions, mismatches, and other stacking perturbations. DNA repair proteins containing [4Fe4S] clusters can take advantage of DNA charge transport (CT) chemistry to scan the genome for mistakes more efficiently. Here we examine the effective length over which charge can be transported along DNA between these repair proteins. We define the effective CT distance as the length of DNA within which two proteins are able to influence their ensemble affinity to the DNA duplex via CT. Endonuclease III, a DNA repair glycosylase containing a [4Fe4S] cluster, was incubated with DNA duplexes of different lengths (1.5–9 kb), and atomic force microscopy was used to quantify the binding of proteins to these duplexes to determine how the relative protein affinity changes with increasing DNA length. A sharp change in binding slope is observed at 3509 base pairs, or about 1.2 μm, that supports the existence of two regimes for protein binding, one within the range for DNA CT, one outside of the range for CT; DNA CT between the redox proteins bound to DNA effectively decreases the ensemble binding affinity of oxidized and reduced proteins to DNA. Utilizing an Endonuclease III mutant Y82A, which is defective in carrying out DNA CT, shows only one regime for protein binding. Decreasing the temperature to 4 °C or including metallointercalators on the duplex, both of which should enhance base stacking and decrease DNA floppiness, leads to extending the effective length for DNA charge transport to ∼5300 bp or 1.8 μm. These results thus support DNA charge transport between repair proteins over kilobase distances. The results furthermore highlight the ability of DNA repair proteins to search the genome quickly and efficiently using DNA charge transport chemistry.
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spelling pubmed-63467252019-01-28 Effective Distance for DNA-Mediated Charge Transport between Repair Proteins Tse, Edmund C. M. Zwang, Theodore J. Bedoya, Sebastian Barton, Jacqueline K. ACS Cent Sci [Image: see text] The stacked aromatic base pairs within the DNA double helix facilitate charge transport down its length in the absence of lesions, mismatches, and other stacking perturbations. DNA repair proteins containing [4Fe4S] clusters can take advantage of DNA charge transport (CT) chemistry to scan the genome for mistakes more efficiently. Here we examine the effective length over which charge can be transported along DNA between these repair proteins. We define the effective CT distance as the length of DNA within which two proteins are able to influence their ensemble affinity to the DNA duplex via CT. Endonuclease III, a DNA repair glycosylase containing a [4Fe4S] cluster, was incubated with DNA duplexes of different lengths (1.5–9 kb), and atomic force microscopy was used to quantify the binding of proteins to these duplexes to determine how the relative protein affinity changes with increasing DNA length. A sharp change in binding slope is observed at 3509 base pairs, or about 1.2 μm, that supports the existence of two regimes for protein binding, one within the range for DNA CT, one outside of the range for CT; DNA CT between the redox proteins bound to DNA effectively decreases the ensemble binding affinity of oxidized and reduced proteins to DNA. Utilizing an Endonuclease III mutant Y82A, which is defective in carrying out DNA CT, shows only one regime for protein binding. Decreasing the temperature to 4 °C or including metallointercalators on the duplex, both of which should enhance base stacking and decrease DNA floppiness, leads to extending the effective length for DNA charge transport to ∼5300 bp or 1.8 μm. These results thus support DNA charge transport between repair proteins over kilobase distances. The results furthermore highlight the ability of DNA repair proteins to search the genome quickly and efficiently using DNA charge transport chemistry. American Chemical Society 2019-01-11 2019-01-23 /pmc/articles/PMC6346725/ /pubmed/30693326 http://dx.doi.org/10.1021/acscentsci.8b00566 Text en Copyright © 2019 American Chemical Society This is an open access article published under an ACS AuthorChoice License (http://pubs.acs.org/page/policy/authorchoice_termsofuse.html) , which permits copying and redistribution of the article or any adaptations for non-commercial purposes.
spellingShingle Tse, Edmund C. M.
Zwang, Theodore J.
Bedoya, Sebastian
Barton, Jacqueline K.
Effective Distance for DNA-Mediated Charge Transport between Repair Proteins
title Effective Distance for DNA-Mediated Charge Transport between Repair Proteins
title_full Effective Distance for DNA-Mediated Charge Transport between Repair Proteins
title_fullStr Effective Distance for DNA-Mediated Charge Transport between Repair Proteins
title_full_unstemmed Effective Distance for DNA-Mediated Charge Transport between Repair Proteins
title_short Effective Distance for DNA-Mediated Charge Transport between Repair Proteins
title_sort effective distance for dna-mediated charge transport between repair proteins
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6346725/
https://www.ncbi.nlm.nih.gov/pubmed/30693326
http://dx.doi.org/10.1021/acscentsci.8b00566
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