PMID: 108675Mar 1, 1979

Isolation and characterization of purine-nucleoside phosphorylase-deficient T-lymphoma cells and secondary mutants with altered ribonucleotide reductase: genetic model for immunodeficiency disease

Proceedings of the National Academy of Sciences of the United States of America
B UllmanD W Martin

Abstract

The inherited deficiency of purine-nucleoside phosphorylase (PNPase; purine-nucleoside:orthophosphate ribosyltransferase, EC 2.4.2.1) in humans is associated with a severe deficiency of the T lymphocytes of the immune system. Because of the unsatisfactory nature of previously described model systems, we have selected, cloned, and characterized a mutant mouse T cell lymphoma (S49) completely deficient in PNPase. Of the four substrates of PNPase, only deoxyguanosine at low concentrations is toxic to the PNPase-deficient (NSU-1) cells. In order to delineate the biochemical processes necessary for the sensitivity of the NSU-1 cells to deoxyguanosine, we have isolated a series of secondary mutants resistant to deoxyguanosine from the PNPase-deficient line. One of these mutants is defective in its ability to transport deoxyguanosine into the cell. A second type of mutant cannot phosphorylate the deoxyguanosine and is totally deficient in deoxycytidine kinase activity. A third type of mutant (NSU-1-dGuo-L) can both transport and phosphorylate deoxyguanosine and accumulates dGTP. However, unlike its parent, NSU-1-dGuo-L does not become depleted of dCTP and TTP when exposed to exogenous deoxyguanosine. This observation is accounted for ...Continue Reading

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Citations

Oct 1, 1980·European Journal of Pediatrics·K O Raivio
Sep 1, 1985·Somatic Cell and Molecular Genetics·G WeinbergD W Martin
Oct 14, 1985·Mechanisms of Ageing and Development·J E Dick, J A Wright
Jan 1, 1980·Advances in Enzyme Regulation·L J GudasD W Martin
Aug 2, 1984·The New England Journal of Medicine·F S RosenR J Wedgwood
Nov 15, 1984·The New England Journal of Medicine·M SeligmannT J Spira
Apr 1, 1981·Proceedings of the National Academy of Sciences of the United States of America·G WeinbergD W Martin
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Jul 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J M GoddardD W Martin
Jul 25, 1984·Nucleic Acids Research·S R WilliamsD W Martin
Jun 23, 1993·Annals of the New York Academy of Sciences·V St Georgiev
Sep 1, 1984·The Journal of Clinical Investigation·B Ullman, D W Martin
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Nov 1, 1986·The Journal of Clinical Investigation·G J Mann, R M Fox
Apr 5, 2001·Proceedings of the National Academy of Sciences of the United States of America·G A KicskaH L Kaufman
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Jan 1, 1982·Environmental Mutagenesis·B A Kunz
Nov 11, 2019·Journal of Clinical Immunology·Yael Dinur SchejterIrina Zaidman
Aug 17, 2020·Nucleic Acids Research·Roman S Iwasaki, Robert T Batey

Related Concepts

Deoxyribonucleotides
Immunologic Deficiency Syndromes
Lymphoma
Neoplasms, Experimental
Pentosyltransferase
Nicotinamide Riboside Phosphorylase
Ribonucleotide Reductase

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