Effect of folylpolyglutamate synthetase (FPGS) modulation on p53 and p21. p53 is integrally involved in cell cycle control, DNA repair, and apoptosis50 while p21 is a member of the cyclin dependent kinase inhibitor family, which inhibits G1 and S phase progression.51 p53 promotes cell cycle arrest in late G1 through upregulation of p21 in response to cell injury, thereby allowing time for repair, whereas in the event that DNA damage is more severe and non-reparable, p53 performs its alternative role of moving the cell into apoptosis.50 FPGS overexpression (FPGS-S) downregulated, whereas FPGS inhibition (FPGS-AS) upregulated, p53 and p21 protein expression compared with endogenous FPGS (vector alone (VA)) in HCT116 cells (densitometry of bands: p53:β-actin ratio 1.9 (FPGS-S) v 3.1 (VA) v 4.1 (FPGS-AS); p21:β-actin ratio 1.7 (FPGS-S) v 2.5 (VA) v 3.2 (FPGS-AS)).