Schematic illustrating the proposed mechanism of how chronic inflammation may induce microsatellite instability in ulcerative colitis. Among the factors released by inflammatory cells in ulcerative colitis are proinflammatory cytokines, ROS, and NO. Hofseth et al. (9) propose and provide evidence for inflammation-associated increases in the levels of the DNA repair enzymes AAG and APE1, which in turn produce instability at microsatellite sequences in various types of cells in the affected tissue (shown here as a colonic crypt stem cell). The exact mechanism through which AAG and APE1 produce MSI remains to be elucidated, but it may be related to imbalances in the components of the base excision repair pathway and the accumulation of mutagenic repair intermediates.