POLQ, also known as DNA polymerase theta, is a key enzyme in DNA double-strand break (DSB) repair, mainly involved in the microhomology-mediated end-joining (MMEJ) pathway. It has both helicase and polymerase activities, playing a crucial role in maintaining genome stability. Genetic models, such as gene knockout in cells, are valuable for studying its functions [1,2,4,5,6].

POLQ-deficient cells accumulate post-replicative ssDNA gaps upon BRCA1/2 loss or PARP inhibitor treatment, indicating its role in post-replicative gap sealing. In HR-deficient pancreatic adenocarcinoma, POLQ knockdown is synthetically lethal with HR gene mutations, and it also activates the cGAS-STING signaling pathway, enhancing tumor immune infiltration. In gastric cancer, POLQ knockdown suppresses the stemness of cancer cells and their resistance to ferroptosis. In telomere-driven crisis models, POLQ-/-cells show unique telomere-related phenotypes and reduced chromosomal abnormalities [1,2,3,4].

In conclusion, POLQ is essential for maintaining genome stability through its role in DSB repair and post-replicative gap sealing. Studies using POLQ-deficient models have revealed its significance in cancer-related processes, such as synthetic lethality in HR-deficient cancers, regulation of cancer cell stemness and ferroptosis resistance, and influence on telomere-related genomic stability. These findings provide potential therapeutic targets for cancer treatment [1,2,3,4].