GSE50692
Uracil DNA glycosylase (UNG) loss enhances DNA double strand break formation in human cancer cells exposed to pemetrexed
To test the effects of uracil DNA glycosylase (UNG) loss on the formation of double strand breaks (DSBs) by the anti-cancer agent pemetrexed, we performed ChIP-seq for serine 139-phosphorylated H2AX (gammaH2AX), a marker of DSBs, in human cells wild-type or deficient for UNG in combination with pemetrexed treatment.  UNG deficiency results in an increase in DSBs upon pemetrexed treatment, and we found that pemetrexed treatment induces DSBs at different genomic locations in UNG wild-type and knockout cells.  Similar results were observed upon cisplatin treatment of UNG wild-type and knockout cells, and the genomic locations of DSBs were distinct between pemetrexed-treated and cisplatin-treated samples.  Taken together, our results suggest differential mechanisms for DSB formation in UNG-competent and UNG-deficient cells. Overall design: The genomic distribution of gammaH2AX in UNG WT and KO cells treated with pemetrexed or cisplatin was determined by ChIP-seq