The interest in Polθ as a therapeutic target in cancer has been piqued by a number of observations including synthetic lethal interactions between loss of the POLQ gene and deficiencies in DNA repair-related tumour suppressor genes that control DSB repair/HR, including BRCA1, BRCA2, ATM and FANCD2, observations perhaps best explained by the role TMEJ plays as a backup pathway in the absence of HR7,13,16–18. The gene discussed is BRCA1; the disease is cancer.