Key enzyme in folate metabolism. Contributes to the de novo mitochondrial thymidylate biosynthesis pathway. Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its own mRNA (By similarity). (6S)-5,6,7,8-tetrahydrofolate + NADP(+) = 7,8-dihydrofolate + H(+) + NADPH Cofactor biosynthesis; tetrahydrofolate biosynthesis; 5,6,7,8-tetrahydrofolate from 7,8-dihydrofolate: step 1/1. Homodimer. The sequence shown is that of A3-35. The two clones A3-35 and MQ19-97 represent allelic forms. They differ in their drug sensitivities, possibly because of the difference at position 22. Overexpression of the dihydrofolate gene (generally involving gene amplification) results in resistance to the antitumor antifolate drugs methotrexate (MTX) and methasquin. Belongs to the dihydrofolate reductase family.