DNA Polymerase θ (POLQ) (153-5-1) Mouse mAb #48160

Mammalian cells undergo DNA damage in response to various intrinsic and extrinsic forces, and signaling pathways are in place to sense and repair damaged DNA to avoid genome instability and mutation. Repair of toxic DNA double-strand breaks (DSBs) can occur through several pathways, and pathway choice may depend on the cell cycle phase and the nature of the DSB (1). The two main pathways for DSB repair are classical non-homologous end joining (C-NHEJ) and homologous recombination (HR). In addition, three error-prone pathways, single-strand annealing (SSA), microhomology-mediated end-joining (MMEJ), and polymerase theta-mediated end-joining (TMEJ) have been described (2).

Exploiting DNA repair deficiencies in human cancer by targeting intact DNA repair pathways is a promising approach to cancer therapy. This approach has been successful with the use of poly (ADP-ribose) polymerase (PARP) inhibitors in HR-deficient cancer (3).

DNA polymerase θ, encoded by the POLQ gene, is a 290 kDa protein with an N-terminal helicase-like domain and a C-terminal DNA polymerase domain (4). ZEB1, an epithelial-mesenchymal transition (EMT) transcription factor, has been shown to regulate TMEJ by suppressing POLQ expression (5). DNA polymerase θ is essential in TMEJ and is, therefore, an important target for drug development in HR-deficient cancers (6,7). Several inhibitors of DNA polymerase θ are under investigation in pre-clinical and clinical trials (8,9).