A huge shoutout to our former grad student Susanne Kassube (now PI) for leading our lab’s original study back in 2013 and setting the stage for this work. If you’re interested, check out our preprint for more details and stay tuned for the full paper! 7/7

Beyond a role in slowing down Pol II elongation, RECQL5 is known to decrease transcription stress. We propose that RECQL5 may help restart transcription from stalled Pol II by allosterically modulating Pol II’s translocation state. 6/7

Nucleotide binding (AMPPNP or ADP) causes the RECQL5 helicase domain to undergo a conformational change, pulling on the DNA to induce Pol II to shift to a post-translocation state. Meanwhile, the IRI module seems to serve as a stable anchor for RECQL5 binding. 5/7

The high resolution of our structures also enabled us to ask how RECQL5 affects Pol II, in particular its translocation state on a DNA/RNA scaffold. We found that Pol II occupies different translocation states when RECQL5 helicase is in its apo vs. nucleotide-bound form. 4/7

We report high-resolution structures of Pol II elongation complexes with RECQL5, visualizing interactions between RECQL5, Pol II, and DNA, confirming its role as a transcriptional roadblock. This required extensive data processing, as RECQL5 is very flexible! 3/7

RecQ helicases help safeguard genome stability. In this family, RECQL5 stands out as the only one to interact with and inhibit RNA Pol II, and it’s been shown to help decrease transcription stress. We used cryo-EM to investigate the molecular basis for this mechanism. 2/7

The recording of the talks is now available at youtube.com/playlist?lis...