Figure 6.

Model for the interface between USP14 and DDR in NSCLC. Genotoxic stress following IR treatment in NSCLC cells induces USP14 expression and its recruitment to DSB sites. USP14 regulates RNF168 and NHEJ core complex assembly to keep NHEJ under check and also maintains proficient HR. Optimal function of NHEJ and HR enables the cells to more efficiently repair DSBs induced by IR. Targeting USP14 causes up-regulation of NHEJ and inhibits HR. Excessive NHEJ is mutagenic, causing genomic instability and therefore, it is detrimental to the cells. Importantly, DSBs cannot be repaired efficiently in the absence of HR, thus, leading to increased cell death in response to IR. Those in red refer to inhibitory or downregulated, and in green refer to upregulated.