title: An ERCC1 splicing variant involving the 5'-UTR of the mRNA may have a transcriptional modulatory function.
abstract: Human ovarian cancer cells and tissues were examined for the presence or absence of a 42-bp splicing variant of ERCC1 gene, and for a possible functional role of this 42-bp sequence. This specific sequence exists in exon I, the 5'-UTR of the gene. Loss of this 42-bp sequence was associated with increased ERCC1 mRNA expression, in an assessment of 121 ovarian cancer specimens (p2<10(-6)). In cells in tissue culture, the absence of the 42-bp segment was associated with a twofold increased ability to drive transcription in a Luciferase reporter system. Protein can be demonstrated in ovarian cancer cells based on EMSA analysis. Computer analysis shows that this 42-bp sequence contains several binding sites, including a core-binding domain for protein RFX1, transcriptional repressor. These preliminary results lay the groundwork in determination of potential roles for a negative regulatory element in NER repair pathway.
authors.affiliation: West Virginia University, Mary Babb Randolph Cancer Center, Robert C. Byrd Health Sciences Center, 1801 Health Sciences South, P.O. Box 9300, Morgantown, WV 26506-9300, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Yu
authors.forename: K
authors.initials: K
authors.lastname: Thornton
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: H
authors.initials: H
authors.lastname: Kotz
authors.forename: E
authors.initials: E
authors.lastname: Reed
mesh_terms: D020121:5' Untranslated Regions / Q000378:metabolism / Q000502:physiology*; D017398:Alternative Splicing; D001483:Base Sequence; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D004720:Endonucleases; D005091:Exons; D005260:Female; D006801:Humans; D008969:Molecular Sequence Data; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism / Q000502:physiology; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D020121:5' Untranslated Regions; D004268:DNA-Binding Proteins; D011506:Proteins; C000605537:RFX1 protein, human; D012333:RNA, Messenger; D000071701:Regulatory Factor X Transcription Factors; D000071716:Regulatory Factor X1; D012097:Repressor Proteins; D014157:Transcription Factors; C071447:ERCC1 protein, human; D004720:Endonucleases