DNA polymerase θ (POLQ): A druggable DNA polymerase for homologous recombination-deficient cancer cells

Irregularities in the DNA repair pathways are frequently observed in cancer. Dysregulated DNA repair pathways support growth advantages to tumor cells. DNA polymerase-theta (POLQ) is an error-prone DNA polymerase involved in double-strand break repair through microhomology-mediated end joining (MMEJ). POLQ also mediates translesion DNA synthesis and it is largely not expressed in normal cells. POLQ is overexpressed in a range of cancer cells, including homologous recombination (HR) deficient cancer cells. In HR deficient cells, MMEJ is crucial as a backup DNA repair pathway, indicating the indispensable role of POLQ-mediated MMEJ in HR deficient cancer cells. In addition, POLQ is synthetic lethal with a number of oncogenes. This viewpoint highlights the potential role of POLQ as a new target in the treatment of HR-deficient tumors and aims to develop enthusiasm to introduce fundamental aspects of Molecular Biology and Biochemistry to basic research related to Molecular Life Sciences, Cell Biology and Genetics in Sri Lanka as Molecular Biology and Biochemistry fundamentals can still do wonders in modern research.

Automated summary

Irregularities in DNA repair pathways are common in cancer, with POLQ being an overexpressed DNA polymerase in tumor cells. In HR-deficient cells, POLQ-mediated microhomology-mediated end joining (MMEJ) is an important backup repair pathway.