Light‐Wavelength‐Based Quantitative Control of Dihydrofolate Reductase Activity by Using a Photochromic Isostere of an Inhibitor

ChemBioChem ◽  
2019 ◽  
Vol 20 (11) ◽  
pp. 1382-1386
Author(s):  
Takato Mashita ◽  
Toshiyuki Kowada ◽  
Hiroto Takahashi ◽  
Toshitaka Matsui ◽  
Shin Mizukami
Keyword(s):  
Dihydrofolate Reductase ◽  
Reductase Activity ◽  
Light Wavelength

Direct demonstration of genetic alterations at the dihydrofolate reductase locus after gamma irradiation

1982 ◽  
Vol 2 (1) ◽  
pp. 93-96
Author(s):  
L H Graf ◽  
L A Chasin
Keyword(s):  
Dihydrofolate Reductase ◽  
Gamma Ray ◽  
Reductase Activity ◽  
Chinese Hamster Ovary Cells ◽  
Cdna Probe ◽  
Chinese Hamster ◽  
Genetic Alterations ◽  
Ovary Cells ◽  
Direct Demonstration ◽  
Dna Deletions

Gamma ray-induced mutants of Chinese hamster ovary cells lacking dihydrofolate reductase activity were screened for DNA sequence changes at the locus specifying this activity by using a cloned cDNA probe. Two of nine mutants screened displayed an altered restriction fragment pattern suggesting the occurrence of DNA deletions or rearrangements.

Heterogeneity in the specific activity and methotrexate sensitivity of dihydrofolate reductase from blast cells of acute myelogenous leukemia patients.

1985 ◽  
Vol 3 (11) ◽  
pp. 1545-1552 ◽  
Author(s):  
S Dedhar ◽  
D Hartley ◽  
D Fitz-Gibbons ◽  
G Phillips ◽  
J H Goldie
Keyword(s):  
Dihydrofolate Reductase ◽  
Acute Myelogenous Leukemia ◽  
Specific Activity ◽  
Reductase Activity ◽  
Myelogenous Leukemia ◽  
Mechanisms Of Resistance ◽  
Clinical Resistance ◽  
Dihydrofolate Reductases ◽  
Acute Myelogenous ◽  
Blast Cells

Dihydrofolate reductase activity was found to be highly heterogeneous in terms of its specific activity and methotrexate sensitivity in the blast cells of patients with acute myelogenous leukemia. None of the patients had previously been treated with methotrexate (MTX). The blast cells of four of 12 patients studied contained methotrexate-insensitive forms of dihydrofolate reductase, and the blast cells of three (distinct from the four mentioned previously) of the 12 had significantly higher dihydrofolate reductase activities than the rest. The presence of MTX-insensitive dihydrofolate reductases and high levels of enzyme activity represent intrinsic mechanisms of resistance and may explain the apparent clinical resistance of acute myelogenous leukemia to methotrexate.

scholarly journals Direct demonstration of genetic alterations at the dihydrofolate reductase locus after gamma irradiation.

1982 ◽  
Vol 2 (1) ◽  
pp. 93-96 ◽  
Author(s):  
L H Graf ◽  
L A Chasin
Keyword(s):  
Dihydrofolate Reductase ◽  
Gamma Ray ◽  
Reductase Activity ◽  
Chinese Hamster Ovary Cells ◽  
Cdna Probe ◽  
Chinese Hamster ◽  
Genetic Alterations ◽  
Ovary Cells ◽  
Direct Demonstration ◽  
Dna Deletions

Gamma ray-induced mutants of Chinese hamster ovary cells lacking dihydrofolate reductase activity were screened for DNA sequence changes at the locus specifying this activity by using a cloned cDNA probe. Two of nine mutants screened displayed an altered restriction fragment pattern suggesting the occurrence of DNA deletions or rearrangements.

scholarly journals Flavin-Dependent Thymidylate Synthase ThyX Activity: Implications for the Folate Cycle in Bacteria

2007 ◽  
Vol 189 (23) ◽  
pp. 8537-8545 ◽  
Author(s):  
Damien Leduc ◽  
Frédéric Escartin ◽  
H. Frederik Nijhout ◽  
Michael C. Reed ◽  
Ursula Liebl ◽  
...  
Keyword(s):  
Dihydrofolate Reductase ◽  
Thymidylate Synthase ◽  
Insertional Mutagenesis ◽  
Rhodobacter Capsulatus ◽  
De Novo ◽  
Reductase Activity ◽  
Direct Proof ◽  
Cellular Functions ◽  
Thymidylate Synthesis

ABSTRACT Although flavin-dependent ThyX proteins show thymidylate synthase activity in vitro and functionally complement thyA defects in heterologous systems, direct proof of their cellular functions is missing. Using insertional mutagenesis of Rhodobacter capsulatus thyX, we constructed the first defined thyX inactivation mutant. Phenotypic analyses of the obtained mutant strain confirmed that R. capsulatus ThyX is required for de novo thymidylate synthesis. Full complementation of the R. capsulatus thyX::spec strain to thymidine prototrophy required not only the canonical thymidylate synthase ThyA but also the dihydrofolate reductase FolA. Strikingly, we also found that addition of exogenous methylenetetrahydrofolate transiently inhibited the growth of the different Rhodobacter strains used in this work. To rationalize these experimental results, we used a mathematical model of bacterial folate metabolism. This model suggests that a very low dihydrofolate reductase activity is enough to rescue significant thymidylate synthesis in the presence of ThyX proteins and is in agreement with the notion that intracellular accumulation of folates results in growth inhibition. In addition, our observations suggest that the presence of flavin-dependent thymidylate synthase X provides growth benefits under conditions in which the level of reduced folate derivatives is compromised.

Dihydrofolate reductase activity of leukemia L1210 during development of methotrexate resistance

1971 ◽  
Vol 20 (3) ◽  
pp. 716-718 ◽  
Author(s):  
Anthony W. Schrecker ◽  
J.A.R. Mead ◽  
Nathaniel H. Greenberg ◽  
Abraham Goldin
Keyword(s):  
Dihydrofolate Reductase ◽  
Reductase Activity ◽  
Methotrexate Resistance
Sign in / Sign up

Export Citation Format

Share Document