Computer based analyses of the 5'-flanking regions of selected genes involved in the nucleotide excision repair complex.
We have previously observed that the mRNA of selected genes involved in nucleotide excision repair appear to be coordinately expressed in human tissues from patients with ovarian cancer, testicular cancer, malignant brain tumors, and other malignancies. Such genes include ERCC1, XPA, XPB, XPD, XPF, and XPG. Coordinate mRNA expression appears to be most impressive in non-malignant tissues. We therefore began to explore possible reasons why such coordinate expression should occur. DNA sequences for the above noted genes were obtained from GeneBank. Two different software programs were applied to the DNA sequence, to the area 5' to the start of exon I of each gene. Analyses were performed by computer. The length of the 5' area assessed, was based on previous reports that determined what portion of the genomic sequence comprised the 5' UTR of the promoter of the respective gene. Based on this approach, potential DNA binding sites for no less than three dozen proteins, were identified in the 5'-flanking region of each of the NER genes studied. For each gene, potential binding sites for activator proteins and for repressor proteins were identified. The 5'-flanking regions for each gene noted above, had binding sites in common for 14 proteins with transcription modulatory activity. Eleven of these proteins are known for activator activity; two are reported to have repressor activity, and one has both repressor and activator function. These data suggest a possible molecular basis for the previously observed coordinate mRNA expression of selected NER genes in human tissue specimens.
Zhong
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X
Medical Ovarian Cancer Section, Medicine Branch, DCS, National Cancer Institute, Bethesda, MD 20892, USA.
Thornton
K
K
Reed
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E
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D001665:Binding Sites / Q000235:genetics; D003201:Computers; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins; D004720:Endonucleases; D005260:Female; D006801:Humans; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics*; D017671:Platinum Compounds / Q000627:therapeutic use; D011506:Proteins / Q000737:chemistry / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D017422:Sequence Analysis, DNA / Q000379:methods*
D033965:Adaptor Protein Complex alpha Subunits; D033942:Adaptor Proteins, Vesicular Transport; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D017671:Platinum Compounds; D011506:Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases