POLQ is a unique gene in higher eukaryotes that encodes for a N-terminal superfamily 2 (SF2) helicase and a C-terminal A-family polymerase also referred to as DNA polymerase θ (Polθ). It has been demonstrated that Polθ is essential to DNA repair mechanisms, as it plays a key role in alternative end-joining (alt-EJ) of double-strand breaks (DSBs) and performs translesion synthesis. In addition, Polθ highly expressed in cancer cells where it confers resistance to ionizing radiation and chemotherapy agents. The aberrant expression of Polθ also promotes survival of homologous recombination (HR) deficient cells, a feature typically observed in cell with mutated BRCA1 or BRCA2 genes. Based on these observations, Polθ is viewed as a promising novel cancer target. As part of our on-going effort to develop novel anti-cancer therapeutic agents, we have been developing novel Polθ inhibitors.
Moulder Center for Drug Discovery Research
Temple University School of Pharmacy
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Philadelphia, PA 19140