FUdR Induction of the X Chromosome Fragile Site: Evidence for the Mechanism of Folic Acid and Thymidine Inhibition

Overview

Journal Am J Hum Genet

Publisher Cell Press

Specialty Genetics

Date 1981 Mar 1

PMID 6452060

Citations 62

Authors

T W Glover

Affiliations

Soon will be listed here.

Abstract

Experiments designed to illuminate the mechanism by which folic acid and thymidine inhibit expression of the Xq28 fragile site in human lymphocytes are described. The fragile site is induced by 5-fluorodeoxyuridine (FUdR), a potent inhibitor of thymidylate synthetase, in the presence of otherwise inhibiting concentrations of folic acid but not in the presence of thymidine. These results indicate that the fragile site is expressed because of depletion of deoxythymidine monophosphate (dTMP) available for DNA synthesis.

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References

Lubs H . A marker X chromosome. Am J Hum Genet. 1969; 21(3):231-44. PMC: 1706424. View

FRIEDKIN M . Thymidylate synthetase. Adv Enzymol Relat Areas Mol Biol. 1973; 38:235-92. DOI: 10.1002/9780470122839.ch5. View

Harvey J, Judge C, Wiener S . Familial X-linked mental retardation with an X chromosome abnormality. J Med Genet. 1977; 14(1):46-50. PMC: 1013506. DOI: 10.1136/jmg.14.1.46. View

Turner G, Till R, Daniel A . Marker X chromosomes, mental retardation and macro-orchidism. N Engl J Med. 1978; 299(26):1472. DOI: 10.1056/NEJM197812282992625. View

Sutherland G . Heritable fragile sites on human chromosomes I. Factors affecting expression in lymphocyte culture. Am J Hum Genet. 1979; 31(2):125-35. PMC: 1685753. View

Sutherland G . Heritable fragile sites on human chromosomes II. Distribution, phenotypic effects, and cytogenetics. Am J Hum Genet. 1979; 31(2):136-48. PMC: 1685761. View

Stoddard G . X-linked mental retardation with macro-orchidism and marker X chromosomes. Hum Genet. 1979; 50(3):247-51. DOI: 10.1007/BF00399389. View

Meuth M, Trudel M . Characterization of a mutator gene in Chinese hamster ovary cells. Proc Natl Acad Sci U S A. 1979; 76(12):6505-9. PMC: 411894. DOI: 10.1073/pnas.76.12.6505. View

Erbe R . Genetic aspects of folate metabolism. Adv Hum Genet. 1979; 9:293-354, 367-9. DOI: 10.1007/978-1-4615-8276-2_5. View

10.

Jacky P, Dill F . Expression in fibroblast culture of the satellited-X chromosome associated with familial sex-linked mental retardation. Hum Genet. 1980; 53(2):267-9. DOI: 10.1007/BF00273509. View

11.

Turner G, Daniel A, Frost M . X-linked mental retardation, macro-orchidism, and the Xq27 fragile site. J Pediatr. 1980; 96(5):837-41. DOI: 10.1016/s0022-3476(80)80552-x. View

12.

Hopkins R, Goodman M . Deoxyribonucleotide pools, base pairing, and sequence configuration affecting bromodeoxyuridine- and 2-aminopurine-induced mutagenesis. Proc Natl Acad Sci U S A. 1980; 77(4):1801-5. PMC: 348595. DOI: 10.1073/pnas.77.4.1801. View

13.

Goulian M, Bleile B, Tseng B . Methotrexate-induced misincorporation of uracil into DNA. Proc Natl Acad Sci U S A. 1980; 77(4):1956-60. PMC: 348628. DOI: 10.1073/pnas.77.4.1956. View