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

[Image: see text] 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.