APEX1 and cancer: Alterations in kcat are relatively modest (a 2.4-fold decrease in activity relative to WT APE1), though the use of pre-steady-state kinetics identified a 4.4-fold decrease in the rate of DNA cleavage by R237C APE1 compared with WT [30], which is well within the range of activity loss by APE1 to result in a 4–6-fold increase in risk of cancer development [29], and a 2.8-fold increase in affinity for DNA [30].