Yu J J, Mu C, Dabholkar M, Guo Y, Bostick-Bruton F, Reed E
Medical Ovarian Cancer Section, Developmental Therapeutics Department, 10/12N226, Medicine Branch, National Cancer Institute, Bethesda, MD 20892, USA.
Int J Mol Med. 1998 Mar;1(3):617-20. doi: 10.3892/ijmm.1.3.617.
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.
可变剪接是抑制全长基因产物功能的一种常见自然机制。我们探究了是否有证据表明ERCC1的可变剪接在核苷酸切除修复中发挥这样的功能。针对一系列人类细胞系和组织，评估了蛋白质和/或mRNA中可变剪接形式与全长形式的比例。通过原子吸收光谱法测量每个细胞系（n = 9）中顺铂-DNA加合物的修复量，并将该比例与之绘制。随着可变剪接蛋白质和/或mRNA百分比的增加，修复的顺铂-DNA加合物量减少。这种负相关关系存在大量离散（r = 0.635），特别是在低修复水平时。这些数据表明ERCC1的可变剪接与细胞修复顺铂-DNA加合物能力的降低之间存在关联。
