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Cited by 417

The DOI matches its Crossref record; 31 of the 31 references it cites were found in a registry or an index.

Isolation and expression of an altered mouse dihydrofolate reductase cDNA.

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Simonsen, C C, Levinson, A D·1983·Proceedings of the National Academy of Sciences

Abstract

We have constructed a cDNA library from a murine cell line expressing high levels of a dihydrofolate reductase (tetrahydrofolate dehydrogenase; 5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase, EC 1.5.1.3) that displays an abnormally low affinity for methotrexate. From this library we have isolated a cDNA clone similar to, but distinguishable from, a cDNA clone previously demonstrated to encode the wild-type enzyme. Analysis of the nucleotide sequence of this cDNA clone allows us to predict that the altered dihydrofolate reductase differs from the wild-type enzyme at a single amino acid, reflecting the substitution of an arginine for a leucine residue in a region of the polypeptide thought to form a hydrophobic pocket essential for inhibitor binding. To confirm that this substitution was responsible for the altered properties of the enzyme, we genetically localized the region of the cDNA that specified resistance to methotrexate by in vitro recombination. These results reveal that a single nucleotide change in the codon specifying amino acid 22 of the enzyme was sufficient to alter the methotrexate sensitivity of the enzyme. We demonstrate that this altered gene can be employed as a dominant selectable marker in cultured cells expressing normal levels of wild-type dihydrofolate reductase.

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Metadata

Authors
Simonsen, C. C., & Levinson, A. D.
Venue
Proceedings of the National Academy of Sciences
Published
1983-05
Volume
80
Issue
9
Pages
2495-2499
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2042526641
Cited by
417
References
31
FWCI
9.05
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Isolation and expression of an altered mouse dihydrofolate reductase cDNA. https://app.cochat.ai/papers/10.1073/pnas.80.9.2495
The paper
Simonsen, C. C., & Levinson, A. D. (1983). Isolation and expression of an altered mouse dihydrofolate reductase cDNA. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.80.9.2495

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