Mutation frequency decline revisited

'Mutation frequency decline' (MFD) was discovered about forty years ago, and described as the disappearance of a particular class of ultraviolet light-induced mutations in Escherichia coli that occurred whenever protein synthesis was briefly inhibited immediately after irradiation. Later, MFD was interpreted as an excision repair anomaly uniquely affecting nonsense suppressor mutations induced in certain tRNA genes. Never fully understood, MFD has recently been linked to the newly discovered transcription-coupled rapid repair of ultraviolet damage on the template strand of active genes. This article recalls the emergence and development of the MFD story, and offers a new way to explain it and its relation to strand-specific excision repair.