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- Publisher Website: 10.1021/jacs.7b07230
- Scopus: eid_2-s2.0-85029599957
- PMID: 28817778
- WOS: WOS:000411043900067
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Article: The Oxidation State of [4Fe4S] Clusters Modulates the DNA-Binding Affinity of DNA Repair Proteins
Title | The Oxidation State of [4Fe4S] Clusters Modulates the DNA-Binding Affinity of DNA Repair Proteins |
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Authors | |
Issue Date | 2017 |
Publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html |
Citation | Journal of the American Chemical Society, 2017, v. 139 n. 36, p. 12784-12792 How to Cite? |
Abstract | A central question important to understanding DNA repair is how certain proteins are able to search for, detect, and fix DNA damage on a biologically relevant time scale. A feature of many base excision repair proteins is that they contain [4Fe4S] clusters that may aid their search for lesions. In this paper, we establish the importance of the oxidation state of the redox-active [4Fe4S] cluster in the DNA damage detection process. We utilize DNA-modified electrodes to generate repair proteins with [4Fe4S] clusters in the 2+ and 3+ states by bulk electrolysis under an O2-free atmosphere. Anaerobic microscale thermophoresis results indicate that proteins carrying [4Fe4S]3+ clusters bind to DNA 550 times more tightly than those with [4Fe4S]2+ clusters. The measured increase in DNA-binding affinity matches the calculated affinity change associated with the redox potential shift observed for [4Fe4S] cluster proteins upon binding to DNA. We further devise an electrostatic model that shows this change in DNA-binding affinity of these proteins can be fully explained by the differences in electrostatic interactions between DNA and the [4Fe4S] cluster in the reduced versus oxidized state. We then utilize atomic force microscopy (AFM) to demonstrate that the redox state of the [4Fe4S] clusters regulates the ability of two DNA repair proteins, Endonuclease III and DinG, to bind preferentially to DNA duplexes containing a single site of DNA damage (here a base mismatch) which inhibits DNA charge transport. Together, these results show that the reduction and oxidation of [4Fe4S] clusters through DNA-mediated charge transport facilitates long-range signaling between [4Fe4S] repair proteins. The redox-modulated change in DNA-binding affinity regulates the ability of [4Fe4S] repair proteins to collaborate in the lesion detection process. |
Persistent Identifier | http://hdl.handle.net/10722/269302 |
ISSN | 2023 Impact Factor: 14.4 2023 SCImago Journal Rankings: 5.489 |
PubMed Central ID | |
ISI Accession Number ID |
DC Field | Value | Language |
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dc.contributor.author | Tse, CME | - |
dc.contributor.author | Zwang, TJ | - |
dc.contributor.author | Barton, JK | - |
dc.date.accessioned | 2019-04-23T03:56:34Z | - |
dc.date.available | 2019-04-23T03:56:34Z | - |
dc.date.issued | 2017 | - |
dc.identifier.citation | Journal of the American Chemical Society, 2017, v. 139 n. 36, p. 12784-12792 | - |
dc.identifier.issn | 0002-7863 | - |
dc.identifier.uri | http://hdl.handle.net/10722/269302 | - |
dc.description.abstract | A central question important to understanding DNA repair is how certain proteins are able to search for, detect, and fix DNA damage on a biologically relevant time scale. A feature of many base excision repair proteins is that they contain [4Fe4S] clusters that may aid their search for lesions. In this paper, we establish the importance of the oxidation state of the redox-active [4Fe4S] cluster in the DNA damage detection process. We utilize DNA-modified electrodes to generate repair proteins with [4Fe4S] clusters in the 2+ and 3+ states by bulk electrolysis under an O2-free atmosphere. Anaerobic microscale thermophoresis results indicate that proteins carrying [4Fe4S]3+ clusters bind to DNA 550 times more tightly than those with [4Fe4S]2+ clusters. The measured increase in DNA-binding affinity matches the calculated affinity change associated with the redox potential shift observed for [4Fe4S] cluster proteins upon binding to DNA. We further devise an electrostatic model that shows this change in DNA-binding affinity of these proteins can be fully explained by the differences in electrostatic interactions between DNA and the [4Fe4S] cluster in the reduced versus oxidized state. We then utilize atomic force microscopy (AFM) to demonstrate that the redox state of the [4Fe4S] clusters regulates the ability of two DNA repair proteins, Endonuclease III and DinG, to bind preferentially to DNA duplexes containing a single site of DNA damage (here a base mismatch) which inhibits DNA charge transport. Together, these results show that the reduction and oxidation of [4Fe4S] clusters through DNA-mediated charge transport facilitates long-range signaling between [4Fe4S] repair proteins. The redox-modulated change in DNA-binding affinity regulates the ability of [4Fe4S] repair proteins to collaborate in the lesion detection process. | - |
dc.language | eng | - |
dc.publisher | American Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/jacsat/index.html | - |
dc.relation.ispartof | Journal of the American Chemical Society | - |
dc.title | The Oxidation State of [4Fe4S] Clusters Modulates the DNA-Binding Affinity of DNA Repair Proteins | - |
dc.type | Article | - |
dc.identifier.email | Tse, CME: ecmtse@hku.hk | - |
dc.identifier.authority | Tse, CME=rp02452 | - |
dc.description.nature | link_to_OA_fulltext | - |
dc.identifier.doi | 10.1021/jacs.7b07230 | - |
dc.identifier.pmid | 28817778 | - |
dc.identifier.pmcid | PMC5929122 | - |
dc.identifier.scopus | eid_2-s2.0-85029599957 | - |
dc.identifier.hkuros | 297271 | - |
dc.identifier.hkuros | 293826 | - |
dc.identifier.volume | 139 | - |
dc.identifier.issue | 36 | - |
dc.identifier.spage | 12784 | - |
dc.identifier.epage | 12792 | - |
dc.identifier.isi | WOS:000411043900067 | - |
dc.publisher.place | United States | - |
dc.identifier.issnl | 0002-7863 | - |