Figure 3.

Novel role of NHEJ in formation of ecDNA in therapeutic resistance of cancers. ecDNA-containing cancer cells express higher level of proteins associated with NHEJ, which can promote the repair of DNA double-strand break (DSB) induced by radiotherapy and chemotherapy, and then lead to the occurrence of therapeutic resistance. However, depletion or inhibition of DNA-PKcs, a key NHEJ protein, can cause the disappearance of ecDNA and the inhibition of DSB repair by NHEJ, thus increase cancer’s sensitivity to treatment and induce cancer cell apoptosis.