POLQ and Fanconi anemia: While POLQ depletion strongly affected ESSC cell viability under treatment with genotoxic agents, low impact on cellular proliferation was observed under normal growth conditions (Figure 4), suggesting that the majority of endogenous DNA damage in ESCC cells can be repaired in the absence of POLQ. FANCD2, another DNA damage repair gene upregulated in ESCC [37], functions in both the Fanconi anemia pathway that repairs inter-strand DNA crosslinks and the homologous recombination (HR) pathway that repairs DNA DSBs [8,38,39].