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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Bibliographic Details
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
Description
Summary: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.