Abstract

Cellular life relies on gene expression, in which DNA is first transcribed into RNA, which is then translated into protein. Transcription is performed by the protein RNA polymerase (RNAP), which interacts with DNA in three sequential events known as initiation, elongation and termination. Mycobacterium tuberculosis (Mtb) represents a global burden to public health, and the transcription factors CarD and RbpA are both essential to Mtb. I have studied the effect of CarD and RbpA on transcription initiation in vitro at the Mtb rrnAP3 promoter. I have shown that CarD stabilizes unwinding of promoter DNA by RNAP using a two-tiered kinetic mechanism. I have also shown that RbpA stabilizes mycobacterial open complexes using a mechanism distinct from that of CarD. Furthermore, RbpA and CarD cooperatively stabilize mycobacterial open complexes, leading to increased transcription. Taken together, these findings lay the groundwork for a mechanistic understanding of gene regulation by essential transcription factors in a bacterium that kills millions of people each year.

Committee Chair

Eric A. Galburt

Committee Members

Barak Cohen, Daved Fremont, Roberto Galletto, Tomasz Heyduk

Comments

Permanent URL: https://doi.org/10.7936/K7K072PZ

Degree

Doctor of Philosophy (PhD)

Author's Department

Biology & Biomedical Sciences (Computational & Molecular Biophysics)

Author's School

Graduate School of Arts and Sciences

Document Type

Dissertation

Date of Award

Winter 12-15-2016

Language

English (en)

Author's ORCID

https://orcid.org/0000-0001-7800-6881

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