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)

Somatic cell hybrids constructed between UV-hypersensitive Chinese hamster ovary cell line UV20 and human lymphocytes were used to examine the influence of a human DNA repair gene, ERCC1, on UV photoproduct repair, mutability at several drug-resistance loci, UV cytotoxicity and UV split-dose recovery. In hybrid cell line 20HL21-4, which contains human chromosome 19, UV-induced mutagenesis at the APRT, HPRT and Na+/K+-ATPase loci was comparable to that in repair-proficient CHO AA8 cells, whereas cell line 20HL21-7, a reduced human-CHO hybrid not containing human chromosome 19, exhibited a hypermutable phenotype at all 3 loci indistinguishable from that of UV20 cells. The response of 20HL21-4 cells to UV cytotoxicity reflected substantial but incomplete restoration of wild-type UV cytotoxic response, whereas responses of UV20 and 20HL21-7 cell lines to UV cytotoxicity were essentially the same, reflecting several-fold UV hypersensitivity. Repair of UV-induced (5-6) cyclobutane dimers and (6-4) photoproducts was examined by radioimmunoassay; (6-4) photoproduct repair was deficient in UV20 and 20HL21-7 cell lines, and intermediate in 20HL21-4 cells relative to wild-type CHO AA8 cells. UV split-dose recovery in 20HL21-4 cells was also intermediate relative to AA8 cells. These results show that the human ERCC1 gene on chromosome 19 is responsible for substantial restoration of UV survival and mutation responses in repair-deficient UV20 cells, but only partially restores (6-4) UV photoproduct repair and UV split-dose recovery.
 ...
PMID:UV mutagenesis, cytotoxicity and split-dose recovery in a human-CHO cell hybrid having intermediate (6-4) photoproduct repair. 254 32

In the Chinese hamster ovary (CHO) cell line, various mutations affecting DNA repair have been obtained. Mutants that belong to 5 genetic complementation groups for ultraviolet (UV) sensitivity and resemble the cells from individuals having the cancer-prone genetic disorder xeroderma pigmentosum (XP) were previously identified. Each mutant is defective in the incision step of nucleotide excision repair and hypersensitive to bulky DNA lesions. These UV mutants can be divided into two subgroups; only Groups 2 and 4 are extremely sensitive to mitomycin C and other DNA cross-linking agents. The clear-cut phenotypes of the CHO mutants have allowed us to construct hybrid cells by fusion with human lymphocytes and thereby identify which human chromosomes carry genes that correct the CHO mutations. The first two mutations analyzed, UV20 (excision-repair deficient; UV Group 2) and EM9, which has a very high frequency of sister chromatid exchange (SCE), are both corrected by chromosome 19. Efforts are underway to isolate complementing repair genes by DNA-mediated gene transfer. The human gene that corrects mutant EM9 and the hamster gene that corrects UV135 (UV Group 5) have been introduced by cotransfer of genomic DNA and the dominant selectable marker gpt (guanine phosphoribosyltransferase) gene. In each case, the DNA repair function was co-selected based on resistance to 5-chlorodeoxyuridine (CldUrd) or repeated UV irradiation, respectively. The presence of a functional human repair gene in the EM9 transformants is shown by the presence of common human DNA sequences on some fragments produced by restriction enzyme cleavage. In UV135, transfer of a repair gene is indicated by a colony distribution containing "jackpots" and by instability of the resistant phenotype.
 ...
PMID:DNA repair genes of mammalian cells. 376 40

Positive selection-negative selection gene targeting was used to disrupt the nucleotide excision repair gene ERCC1 in a Chinese hamster ovary cell line, CHO-K1. Southern and Northern analysis showed that a cell clone isolated by this targeting approach, CHO-7-27, had an ERCC1 gene structure consistent with targeted disruption of ERCC1 exon V, and did not express ERCC1 mRNA. CHO-7-27 was further characterized with respect to UV and mitomycin C sensitivities, and was shown to exhibit severe mutagen sensitivity phenotypes consistent with those of other CHO cell ERCC1 mutants. Mutation frequency experiments showed that CHO-7-27 was UV-hypermutable at the hypoxanthine-guanine phosphoribosyltransferase locus. Experiments assessing host cell reactivation of viral DNA synthesis for UV-irradiated adenovirus showed that CHO7-27 exhibited a severely deficient HCR phenotype similar to that of UV20 cells. Our results demonstrate that CHOK1 cells are hemizygous for the ERCC1 gene, and show that the comparatively mild mutagen sensitivities and lack of severely deficient HCR phenotypes of conventionally derived CHO-K1 ERCC1 mutants, in contrast to the severe phenotypes of CHO-AA8-derived mutants, are not due to any intrinsic genetic differences between CHO-K1 and CHO-AA8 parental cell lines.
 ...
PMID:Survival, mutagenesis, and host cell reactivation in a Chinese hamster ovary cell ERCC1 knock-out mutant. 923 74