Alternative splicing of ERCC1 and cisplatin-DNA adduct repair in human tumor cell lines.
Alternative splicing is a common natural tool for the inhibition of function of full length gene products. We explored whether there was evidence that alternative splicing of ERCC1 may serve such a function for nucleotide excision repair. The ratio of alternatively spliced species to full length species was assessed for the protein and/or for the mRNA, for a series of human cell lines and tissues. This ratio was plotted against the amount of cisplatin-DNA adduct repair in each cell line (n=9), as measured by atomic absorbance spectrometry. As the percentage of alternatively spliced protein and/or mRNA increased, the amount of cisplatin-DNA adduct that was repaired was reduced. This inverse relationship was associated with a substantial amount of scatter (r=0.635), particularly at low levels of repair. These data demonstrate an association between alternative splicing of ERCC1, and reduction in cellular capability to repair cisplatin-DNA adduct.
Yu
J J
JJ
Medical Ovarian Cancer Section, Developmental Therapeutics Department, 10/12N226, Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Mu
C
C
Dabholkar
M
M
Guo
Y
Y
Bostick-Bruton
F
F
Reed
E
E
D017398:Alternative Splicing; D015153:Blotting, Western; D002945:Cisplatin / Q000378:metabolism*; D018736:DNA Adducts / Q000378:metabolism*; D004260:DNA Repair / Q000235:genetics*; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004268:DNA-Binding Proteins; D004720:Endonucleases; D006801:Humans; D016014:Linear Models; D011506:Proteins / Q000032:analysis / Q000235:genetics*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014407:Tumor Cells, Cultured
D018736:DNA Adducts; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D011506:Proteins; D012333:RNA, Messenger; C057270:cisplatin-DNA adduct; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin