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 fu nction of full length gene products. We explored whether there was evi dence that alternative splicing of ERCC1 may serve such a function for nucleotide excision repair. The ratio of alternatively spliced specie s to full length species was assessed for the protein and/or for the m RNA, for a series of human cell lines and tissues. This ratio was plot ted against the amount of cisplatin-DNA adduct repair in each cell lin e (n = 9), as measured by atomic absorbance spectrometry. As the perce ntage of alternatively spliced protein and/or mRNA increased, the amou nt 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.