Document Detail


Antifolate-induced misincorporation of deoxyuridine monophosphate into DNA by cells from patients with the fragile X syndrome.
MedLine Citation:
PMID:  2992271     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The fragile site at Xq27 is expressed in vitro under conditions that lead to decreased intracellular thymidine triphosphate concentration, a condition which has also been shown to promote the misincorporation into DNA of deoxyuridine monophosphate (dUMP) in place of thymidine. We tested for increased whole-cell misincorporation of dUMP as a possible molecular mechanism for the expression of the fragile X abnormality. Neither deoxyuridine triphosphatase nor uracil-DNA-glycosylase, the two enzymes that normally prevent the accumulation of dUMP in DNA, was deficient in fragile X syndrome cells. Misincorporation of dUMP occurred in comparably low levels in both normal and fragile X syndrome lymphoblasts. Although these results provide strong evidence against generalized misincorporation of dUMP in fragile X syndrome cells, a substantial real difference present at Xq27 might not be detected in these studies of whole cells containing the diploid chromosome complement.
Authors:
J C Wang; G P Beardsley; R W Erbe
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  American journal of medical genetics     Volume:  21     ISSN:  0148-7299     ISO Abbreviation:  Am. J. Med. Genet.     Publication Date:  1985 Aug 
Date Detail:
Created Date:  1985-09-24     Completed Date:  1985-09-24     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  7708900     Medline TA:  Am J Med Genet     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  691-6     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
DNA / biosynthesis*
DNA Glycosylases*
Deoxyuracil Nucleotides / metabolism*
Floxuridine / pharmacology
Folic Acid Antagonists / pharmacology*
Fragile X Syndrome / genetics*,  metabolism
Humans
Lymphocytes / metabolism
Male
N-Glycosyl Hydrolases / metabolism
Pyrimethamine / analogs & derivatives,  pharmacology
Pyrophosphatases / metabolism
Sex Chromosome Aberrations / genetics*
Uracil-DNA Glycosidase
Grant Support
ID/Acronym/Agency:
5 T32 GM07748/GM/NIGMS NIH HHS; HD06356/HD/NICHD NIH HHS
Chemical
Reg. No./Substance:
0/Deoxyuracil Nucleotides; 0/Folic Acid Antagonists; 50-91-9/Floxuridine; 58-14-0/Pyrimethamine; 7761-45-7/methodichlorophen; 9007-49-2/DNA; 964-26-1/2'-deoxyuridylic acid; EC 3.2.2.-/DNA Glycosylases; EC 3.2.2.-/N-Glycosyl Hydrolases; EC 3.2.2.-/Uracil-DNA Glycosidase; EC 3.6.1.-/Pyrophosphatases; EC 3.6.1.23/dUTP pyrophosphatase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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