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- W1995146872 abstract "The human glioma cell line M059J is deficient in DNA-dependent protein kinase (DNA-PK) due to a frame-shift mutation in PRKDC, the gene for its catalytic subunit, while cell line M059K, isolated from the same malignant tumor, has normal DNA-PK activity. DNA-PK is required for double-strand DNA break repair, and its absence is responsible for increased radiosensitivity of M059J. We show that transcripts of several melanoma antigen subfamily A (MAGE-A) genes, the expression of which is restricted to tumor and germ-line cells,are present in M059K, but that their expression is strongly downregulated in M059J. Normal levels of MAGE-A expression are restored in the PRKDC-complemented cell line M059J/Fus1, suggesting that the presence of DNA-PK is required for MAGE-A gene transcription. We also show that the MAGE-A1 promoter is methylated in M059J, while the promoter is demethylated in M059K and M059J/Fus1. Other genes, including all three major histocompatibility class I (HLA) genes, BENE, and an unnamed gene related to CNIL(CORNICHON-like), display an opposite expression profile (i.e., they are upregulated in the DNA-PK-deficient cell line, but show low levels of expression in both M059K and in the PRKDC-complemented cell line). For these genes, differential expression does not correlate with DNA methylation in upstream promoter sequences. Our results suggest that the presence of DNA-PK can exert effects on gene expression by various mechanisms and pathways, thus affecting overall cell physiology even in the absence of DNA damage." @default.
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- W1995146872 date "2003-01-01" @default.
- W1995146872 modified "2023-09-26" @default.
- W1995146872 title "Differential Gene Expression in Human Glioma Cells: Correlation With Presence or Absence of DNA-Dependent Protein Kinase" @default.
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- W1995146872 doi "https://doi.org/10.3727/000000003783992306" @default.
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