Metalloregulator CueR biases RNA polymerase’s kinetic sampling of dead-end or open complex to repress or activate transcription

• DOI: 10.1073/pnas.1515231112
• Publication Date: 2015-10-20T12:33:08Z
• Authors: Danya J. Martell; Chandra P. Joshi; Ahmed Gaballa; Ace George Santiago; Tai-Yen Chen; Won Jung; John D. Helmann; Peng Chen
• Keywords: Transcription; RNA polymerase II

Significance MerR-family regulators act on suboptimal promoters to control the transcriptions of genes that help bacteria defend against a diverse set metals and drugs. How they modulate RNA polymerase (RNAP) activity transcription initiation remains unclear, however. Here we show CueR—a Cu + -responsive metalloregulator—biases kinetic sampling RNAP binding events lead two noninterconverting states: dead-end complex repress or an open activate transcription, constituting branched pathway distinct from linear prevalent for at optimal promoters. This mechanistic insight contributes new fundamental knowledge bacterial regulation, may develop antibiotics target this regulation mechanism compromise defenses.