DHFR (dihydrofolate reductase)

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URI: http://hdl.handle.net/2042/66069  |   DOI : https://doi.org/10.4267/2042/66069
Title: DHFR (dihydrofolate reductase)
Author: Krajinovic, Maja; Abaji, Rachid; Sharif-Askari, Bahram
Abstract: Dihydrofolate reductase (DHFR) is a member of the reductase enzyme family, which is ubiquitously expressed in all organisms. Levels of this enzyme peak at the G1/S cell cycle boundary. Autoregulation, through DHFR-RNA interactions, has also been reported. DHFR catalyzes the NADPH dependent reduction of dihydrofolate (DHF) to tetrahydrofolate (THF) needed for several one-carbon transfer reactions in purine and pyrimidine synthesis (Jensen et al 1997, Klon et al 2002). It is also the only enzyme that reduces folic acid, a synthetic vitamin not found in nature, to dihydrofolate (Banka et al. 2011). Reduction of DHFR enzymatic activity diminishes the THF pool inside the cell which slows DNA synthesis and cell proliferation eventually leading to cell death (Assaraf et al 2007, Klon et al 2002, Morales et al 2009). DHFR inhibition is essential to the action of antifolate medications used to treat cancer and some inflammatory diseases. Changes in DHFR expression can affect susceptibility to a variety of diseases dependent on folate status such as spina bifida and cancer. Likewise, human DHFR (hDHFR) has become a major drug target in anticancer therapy (Klon et al 2002, Sharif-Askari et al 2010).
Subject: Dihydrofolate (DHF); Tetrahydrofolate (THF); Folate-dependent enzymes; DNA synthesis; Genes Section; Adolescent; Adult; Brain/*abnormalities; Case-Control Studies; Child; Child, Preschool; Cleft Lip/*genetics; Cleft Palate/*genetics; Female; *Gene Deletion; Gene Frequency; Genetic Association Studies; Humans; Infant; Logistic Models; Male; Middle Aged; Polymerase Chain Reaction; Polymorphism, Genetic/*genetics; Reference Values; Risk Assessment
Publisher: ARMGHM - Atlas Génétique des Cancers
Date: 2016

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