The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products

The newly discovered light-dependent transcription factor CarH uses adenosylcobalamin as a light sensor to regulate expression of protective genes in bacteria upon exposure to sunlight. This use of adenosylcobalamin is a clever adaptation of a classic enzyme cofactor, taking advantage of its photola...

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Main Authors: Jost, Marco, Simpson, Jeffrey H., Drennan, Catherine L.
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: American Chemical Society (ACS) 2017
Online Access:http://hdl.handle.net/1721.1/110584
https://orcid.org/0000-0001-5486-2755
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author Jost, Marco
Simpson, Jeffrey H.
Drennan, Catherine L.
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Jost, Marco
Simpson, Jeffrey H.
Drennan, Catherine L.
author_sort Jost, Marco
collection MIT
description The newly discovered light-dependent transcription factor CarH uses adenosylcobalamin as a light sensor to regulate expression of protective genes in bacteria upon exposure to sunlight. This use of adenosylcobalamin is a clever adaptation of a classic enzyme cofactor, taking advantage of its photolabile Co−C bond. However, it is also puzzling in that photolysis of adenosylcobalamin generates the 5′-deoxyadenosyl radical that could damage DNA. Here, using liquid chromatography and spectroscopic techniques, we demonstrate that CarH suppresses release of the 5′-deoxyadenosyl radical and instead effects conversion to a nonreactive 4′,5′-anhydroadenosine. In this manner, CarH safeguards use of adenosylcobalamin in light-dependent gene regulation.
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spelling mit-1721.1/1105842022-09-29T18:11:55Z The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products Jost, Marco Simpson, Jeffrey H. Drennan, Catherine L. Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Chemistry Jost, Marco Simpson, Jeffrey H. Drennan, Catherine L. The newly discovered light-dependent transcription factor CarH uses adenosylcobalamin as a light sensor to regulate expression of protective genes in bacteria upon exposure to sunlight. This use of adenosylcobalamin is a clever adaptation of a classic enzyme cofactor, taking advantage of its photolabile Co−C bond. However, it is also puzzling in that photolysis of adenosylcobalamin generates the 5′-deoxyadenosyl radical that could damage DNA. Here, using liquid chromatography and spectroscopic techniques, we demonstrate that CarH suppresses release of the 5′-deoxyadenosyl radical and instead effects conversion to a nonreactive 4′,5′-anhydroadenosine. In this manner, CarH safeguards use of adenosylcobalamin in light-dependent gene regulation. National Institutes of Health (U.S.) (Grant GM069857) 2017-07-10T15:22:07Z 2017-07-10T15:22:07Z 2015-05 2015-04 Article http://purl.org/eprint/type/JournalArticle 0006-2960 1520-4995 http://hdl.handle.net/1721.1/110584 Jost, Marco, Jeffrey H. Simpson, and Catherine L. Drennan. “The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products.” Biochemistry 54.21 (2015): 3231–3234. © 2015 American Chemical Society https://orcid.org/0000-0001-5486-2755 en_US http://dx.doi.org/10.1021/acs.biochem.5b00416 Biochemistry Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf American Chemical Society (ACS) ACS
spellingShingle Jost, Marco
Simpson, Jeffrey H.
Drennan, Catherine L.
The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products
title The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products
title_full The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products
title_fullStr The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products
title_full_unstemmed The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products
title_short The Transcription Factor CarH Safeguards Use of Adenosylcobalamin as a Light Sensor by Altering the Photolysis Products
title_sort transcription factor carh safeguards use of adenosylcobalamin as a light sensor by altering the photolysis products
url http://hdl.handle.net/1721.1/110584
https://orcid.org/0000-0001-5486-2755
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