Abstract

Abstract We have developed a panel of human cell lines, each deficient in one of the eleven DNA glycosylase enzymes. To expand background diversity, the same shRNA lentiviruses were also used to develop parallel cell line panels in different tumor backgrounds, including glioma and breast cancer cell lines. Depletion of target mRNA ranged from 67-99% with similar target mRNA depletion across tumor cell backgrounds. Gene expression knockdown was sufficient to functionally diminish enzyme activity, protein levels and mRNA profiling for each exemplified the impact of DNA repair defects on the human transcriptome. As an example of the far reaching potential for a panel of DNA repair deficient cell lines, we show that DNA glycosylase deficiency modulated both the transcriptome and epigenome, implicating some DNA glycosylases in methylation maintenance and genome expression diversity. In addition we demonstrate the impact on DNA repair in glycosylase depleted backgrounds. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3939.

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