Dihydrofolate reductase gene

Gene amplification 1 Many oncogenes are present in multiple copies erbB amplified in certain breast cancers Dihydrofolate reductase genes are amplified in some tumors, leading to drug resistance... 

Kaufman RJ, Brown PC, Schimke RT. Amplified dihydrofolate reductase genes in unstably methotrexate-resistant cells are associated with double minute chromosomes. Proc Natl AcadSci USA 1979 76 5669-5673. 

By growing cells in the presence of increasing concentrations of aminopterin a number of resistant cells lines have been isolated (Hakala and Ishihara, 1962 Littlefield, 1969). These have been characterised as having either an altered permeability to the drug or an altered folate reductase or an increased rate of synthesis and hence increased amounts of the enzyme (Alt et al., 1976), resulting, at least in part, from a selective amplification of the dihydrofolate reductase gene (Alt et al., 1978 Schimke et al., 1988). The problem is considered in more detail in 11.8.1. The importance of the antifolates lies in their role in the HAT selection technique ( 13.5) devised by Szybalski (1962) (see also Szybalski et al., 1962 and Littlefield, 1964) for the isolation of hybrids between mutant cells defective on the one hand in thymidine kinase and on the other hand... 

Navia, M.M. Ruiz, J. Sanchez-Cespedes, J. Vila, J. Detection of dihydrofolate reductase genes by PCR and RFLP. Diagn. Microbiol. Infect. Dis. 2003, 46, 295-298. 

Miller AD, Law MF, Verma IM. 1985. Generation of helper-free amphotropic retroviruses that transduce a dominantacting, methotrexate-resistant dihydrofolate reductase gene. Mol. Cell. Biol. 5 431-37... 

Sultan, A. A., Thathy, V., de Koning-Ward, T. F., and Nussenzweig, V. (2001). Complementation of Plasmodium berghei TRAP knockout parasites using human dihydrofolate reductase gene as a selectable marker. Mol. Biochem. Parasitol. 113,151-156. 

Carothers, A.M., Yuan, W., Hingerty, B.E., Broyde, S., Grunberger, D., and Snyderwine, E.G. (1994) Mutation and repair induced by the car-dnogen 2- (hydroxyamino) -1 -methyl-6-phenylimidazo[4,5 -fejpyridine (N-OH-PhIP) in the dihydrofolate reductase gene of Chinese hamster ovary cells and conformational modeling of the dG-C8-PhIP adduct in DNA. Chem. Res. Toxicol., 7, 209-218. 

May, A., Naim, R.S., Okumoto, D.S., Wassermann, K., Stevnsner, T., Jones, J.C., and Bohr, V.A. (1993) Repair of individual DNA strands in the hamster dihydrofolate reductase gene after treatment with ultraviolet light, alkylating agents, and cisplatin. 

Carothers, A.M., Zhen, W., Mucha, J., Zhang, Y.J., Santella, R.M., Grunberger, D and Bohr, V.A. (1992) DNA strand-specific repair of ( )-3a,4fJ-dihydroxy-1 a,2a-epoxy-l, 2,3,4-tetrahydrobenzo[c]phenanthrene adducts in the hamster dihydrofolate reductase gene. Proc. Natl. Acad. Sci. USA, 89, 11925-11929. 

R.T., Urlaub, G., and Chasin, LA. (1978) Amplified dihydrofolate reductase genes are localized to a homogeneously staining region of a single chromosome in a methotrexate-resistant Chinese hamster ovary cell line. Proc. Natl. Acad. Sci. USA 75 5553-5556. 

Rice GC, Hoy C, Schimke RT (1986) Transient hypoxia enhances the frequency of dihydrofolate reductase gene amplification in Chinese hamster ovary cells. Proc Natl Acad Sci USA 83 5978-5982... 

Yoder, S. S., Robberson, B. L., Leys, E. J., Hook, A. G., Al-Ubaidi, M., Yeung, K-Y., Kellems, R. E., and Berget, S. M., 1983, Control of cellular gene expression during adenovirus infection Induction and shut-off of dihydrofolate reductase gene expression by adenovirus type 2, Mol. Cell Biol. 3 819. 

Bourouis M. and Jarry B. 1983. Vectors containing a prokaryotic dihydrofolate reductase gene transform Drosophila cells to methotrexate-resistance. EMBO J. 2 1099-1104. 

Alt, F. W., Kellems, R. E., Bertino, J. R., and Schimke, R. T., 1978, Selective multiplication of dihydrofolate reductase genes in methotrexate-resistant variants of cultured murine cells, /. Biol. Chem. 253 1357. 

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