Image credit: G. Chandramouly, J. Zhao, S. McDevitt, T. Rusanov, T. Hoang, N. Borisonnik, T. Treddinick, F. W. Lopezcolorado, T. Kent, L. A. Siddique, J. Mallon, J. Huhn, Z. Shoda, E. Kashkina, A. Brambati, J. M. Stark, X. S. Chen, R. T. Pomerantz, PolΘ reverse transcribes RNA and promotes RNA-templated DNA repair. Science Advances 11 June 2021, Volume 7, number 24, eabf1771. DOI: 10.1126/sciadv.abf1771 Figure 3. C and D

Chandramouly et al. reports Polymerase Θ is capable of reverse transcription of RNA in the Journal, Science Advances, Volume 7, number 24, published 11 June 2021. With the aid of Hampton Research crystallization screens, crystals were grown in the presence of 1 mM ddGTP, 200 µM sucrose monolaurate, 1 mM MgCl2, and 20 mM spermine tetrahydrochloride over a reservoir with 20% w/v ethanol. The crystal structure revealed changes in the thumb subdomain and a loop shift in the palm subdomain from RNA interactions with PolΘ. The authors note that the structural reconfiguration is unique to PolΘ and may help explain the unusually promiscuous enzymatic behavior. 

This work suggesting polymerase Θ primary role as a reverse transcriptase opens opportunities to explore polymerase Θ potential as a promising cancer drug target. In cancer cells, the enzyme is highly expressed, and the enzyme’s activity on RNA, leading to DNA repair in cancer cells, promoting cancer cell growth.