Although 5-FU and oxaliplatin generate DNA damage through different mechanisms, they all trigger upregulation of TLS via inducing REV7 expression, suggesting a novel DNA repair mechanism in accordance with DNA damage induced by these drugs and a very promising role of REV7 as a target to overcome 5-FU and oxaliplatin resistance in CRC (Fig. 7). This evidence concerns the gene MAD2L2 and colorectal carcinoma.