Tahir Tahirov, PhD

Warren and Agnes Ritchie Professor in Cancer Research
Professor, UNMC Eppley Institute for Research in Cancer and Allied Diseases
Full member, Fred & Pamela Buffett Cancer Center
Research focus: Structural biology, DNA replication, transcription, biophysics, biochemistry

Send Email

Phone: 402-559-7607

Research 

The Tahirov laboratory focuses on the structural and mechanistic understanding of human DNA replication and transcription complexes. Key breakthroughs include resolving the structure of the regulatory subunits of DNA polymerase δ and revealing a conserved fold across B-family polymerases. This led to the discovery of a polymerase switch mechanism between Pol δ and Pol ζ, mediated by shared accessory subunits.  

We introduced a novel direction examining macromolecular coordination at the replication fork. Central to this is our hypothesis that the p58C subunit of primase coordinates RNA-DNA primer synthesis and handoff to Pol δ and ε. To probe this, we developed a method to synthesize native-like chimeric RNA-DNA primers with 5′-triphosphates. These primers showed altered binding kinetics, polymerase fidelity, and enabled stabilization of elongation complexes for Cryo-EM studies—culminating in the structure of a primosome elongation complex with a 12-mer primer.  

Challenging field norms, we conducted binding and kinetic studies at physiological salt concentrations. This approach revealed increased substrate specificity, dNTP-dependence, and processivity differences, especially for Pol α, whose fidelity we found to depend on the RNA/DNA primer ratio.   

In our transcription study, we explored the structural basis of cooperative DNA binding by oncogenic transcription factors. Structures of complexes involving Runx1, Ets1, CBFβ, c-Myb, and C/EBPβ revealed mechanisms of transcription activation and how oncogenic mutations disrupt them.  

The lab determined the crystal structure of HIV Tat bound to P-TEFb, a major elongation factor hijacked by viruses. A higher-order structure including AFF4 further illuminated transcriptional activation in viral contexts.   

Our work provides a high-resolution structural framework for understanding genome replication and gene regulation, offering potential therapeutic targets for cancer and viral infections.