Document Type


Publication Date



This article is the author’s final published version in Genes, Volume 12, Issue 8, July 2021, Article number 1146.

The published version is available at Copyright © Chen and Pomerantz.


The emergence of precision medicine from the development of Poly (ADP‐ribose) polymerase (PARP) inhibitors that preferentially kill cells defective in homologous recombination has sparked wide interest in identifying and characterizing additional DNA repair enzymes that are synthetic lethal with HR factors. DNA polymerase theta (Polθ) is a validated anti‐cancer drug target that is synthetic lethal with HR factors and other DNA repair proteins and confers cellular resistance to various genotoxic cancer therapies. Since its initial characterization as a helicase‐polymerase fusion protein in 2003, many exciting and unexpected activities of Polθ in microhomology‐mediated end‐joining (MMEJ) and translesion synthesis (TLS) have been discovered. Here, we provide a short review of Polθ‘s DNA repair activities and its potential as a drug target and highlight a recent report that reveals Polθ as a naturally occurring reverse transcriptase (RT) in mammalian cells.

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.





To view the content in your browser, please download Adobe Reader or, alternately,
you may Download the file to your hard drive.

NOTE: The latest versions of Adobe Reader do not support viewing PDF files within Firefox on Mac OS and if you are using a modern (Intel) Mac, there is no official plugin for viewing PDF files within the browser window.