Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.4.2.8 (hypoxanthine-guanine phosphoribosyltransferase)
 2,527 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea (ENU) in three Epstein-Barr virus-transformed human lymphoblastoid cell lines, each with a different DNA repair phenotype. One cell line lacks O6-alkylguanine-DNA alkyltransferase (AGT) activity; another, derived from a patient with xeroderma pigmentosum, complementation group A, lacks nucleotide exicision repair (NER) capability, and the third is competent in both repair functions. ENU-induced toxicity and mutagenicity at the hypoxanthine-guanine phosphoribosyltransferase locus were increased to a similar degree relative to the repair-competent cells in both AGT-deficient and NER-deficient cells. We determined the mutational spectra for ENU by identifying DNA sequence changes at the hypoxanthine-guanine phosphoribosyltransferase locus in at least 26 clones resistant to 6-thioguanine from each cell line. Of the characterized mutations, 89% were single-base pair substitutions. Transitions and transversions were found at AT and GC base pairs in all three cell lines. The biggest difference within the spectra was in the rate of transitions at GC base pairs. Compared to the repair-competent cell line, this mutation was elevated about 8-fold in the AGT-deficient cells and about 3-fold in the NER-deficient cells. We conclude that both AGT and NER play an important role in protecting human cells from the toxic and mutagenic effects of ENU. Furthermore, the mutational spectra suggest that both of these repair systems participate in the repair of O6-ethylguanine adducts.
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PMID:Toxicity, mutagenicity, and mutational spectra of N-ethyl-N-nitrosourea in human cell lines with different DNA repair phenotypes. 165 49

Excision repair deficiencies in groups A and G xeroderma pigmentosum (XP) cells are transiently complemented after microinjection of HeLa poly(A)+RNA, but those in groups D and F are not complemented (Legerski et al., 1984). We tested XP cells belonging to the seven complementation groups, A-G, and Cockayne's syndrome (CS) cells belonging to the two complementation groups, A and B, for transient correction by microinjection of total poly(A)+RNA from HeLa cells. Among the XP cells, unscheduled DNA synthesis (UDS) was increased only in XP-A cells by microinjection of total poly(A)+RNA. However, UDS was increased in XP-E and XP-G cells as well as in XP-A cells by microinjection of concentrated poly(A)+RNA fractionated on a 5-25% sucrose density gradient containing methylmercuric hydroxide. The sizes of XP-E and XP-G mRNA were estimated to be 1.5-2.7 kb and 2.0-3.8 kb, respectively, by comparison to internal marker RNAs including 18S rRNA, 28S rRNA, HPRT mRNA and XPAC mRNA. RNA synthesis recovery after UV exposure in CS cells was not increased by microinjection of either total poly(A)+RNA or fractionated RNA. These results provide estimates of the sizes of XP-E and XP-G proteins and will facilitate molecular cloning of DNA repair genes, especially of XP-E and XP-G genes.
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PMID:Complementation of xeroderma pigmentosum cells by microinjection of mRNA fractionated under denaturing conditions: an estimation of sizes of XP-E and XP-G mRNA. 750 87