Figure 1.

Mechanisms of mismatch repair deficiency leading to cancer development (A) Mismatch repair deficiency is characterized by mutations in or epigenetic inactivation of MMR genes (MLH1, MSH2, PMS2 and MSH6). Normally, proteins encoded by MMR genes detect errors in replication and recruit proteins encoded by MLH and PMS genes. This complex recruits the PCNA/exonuclease complex that excises the mismatch and repairs the DNA through insertion of correct bases. Then, Pol δ is recruited for both leading and lagging strand synthesis, and the ligases catalyze the joining of repaired DNA fragments. (B, C) Accumulation of mutations that are not repaired following MMR deficiency leads to microsatellite extension or shortening through base-pair or three-nucleotide insertion/deletion in microsatellite repeated sequences. This leads to the production of neoantigens if the altered transcript is a coding one. (Created with BioRender.com).