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  • Title: Derepression of HPRT locus on inactive X chromosome of human lymphoblastoid cell line.
    Author: Nadon N, Sekhon G, Brown LJ, Korn N, Petersen JW, Strandtmann J, Chang C, DeMars R.
    Journal: Somat Cell Mol Genet; 1986 Nov; 12(6):541-54. PubMed ID: 3466359.
    Abstract:
    Human XX lymphoblastoid cells with a deletion in the HPRT locus on the active X were exposed to HPRT clone pHPT32. HPRT+ isolates GPT3 and GPT5 lacked pHPT32 DNA, suggesting that their HPRT+ phenotype resulted from expression of a cellular gene. GPT3 mutated to thioguanine resistance at least 100 times more frequently than cells in which the expressed HPRT locus was on the active X. Most GPT3-derived HPRT- had lost one entire X chromosome, indicating that the HPRT+ phenotype of GPT3 resulted from derepression of the HPRT locus on its inactive X. Virtually unchanged G6PD and PGK activities and the presence of a late-replicating X in GPT3 suggest that derepression of the inactive X was not general. Eleven of the GPT3-derived mutants had a tiny centric remnant that may result from a frequently operative mechanism of X chromosome loss. The detection of partial or complete loss of an X by direct selection presents unusual opportunities for genotoxicity detection with human cells.
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