My Blue Dots Blog

POLQ new druggable target identified for cancer therapy

POLQ new druggable target identified for cancer therapy

August 12, 2015

Half of ovarian cancers have abnormal homologous recombination repair mechanism. Loss of homologous recombination

POLQ is a protein that plays a role in the error-prone mirohomology-mediated end-joining (MMEJ) pathway, a pathway required for homologous recombination repair. This study demonstrated that a decreased POLQ expression in epithelial ovarian cancers is associated with increased homologous repair activities. For instance, experiments that decreased the activity ofPOLQ in homologous-proficent cells resulted in an increased homologous recombination activity, and conversely, over expression of POLQ activity resulted in an decreased homologous recombination activity. Furthermore, there is also an inverse relationship between POLQ activity and a protein named RAD51. RAD51 is an important protein that aids in homologous recombination of DNA during double strand break repair. POLQ blocks RAD51’s activity by binding toRAD51 and blocking RAD51-mediated homologous recombination.

This study demonstrated that tumors that are homologous recombination deficient are hypersensitive to the inhibitory activity of POLQ-mediated repair. Therefore, POLQ may be a potential drug target in cancer therapy.

Source: Ceccaldi, Raphael, Jessica C. Liu, and Ravindra Amunugama. “Homologous-recombination-deficient Tumours Are Dependent on Pol-mediated Repair.” Nature 518.7538 (2015): 258-62.

Picture source: