PLX080074

GSE48678: Genome-Wide Transcriptional Effects of the Anti-Cancer Agent Camptothecin

• Organsim human
• Type RNASEQ
• Target gene
• Project ARCHS4

The anti-cancer drug camptothecin inhibits replication and transcription by trapping DNA topoisomerase I (Top1) covalently to DNA in a cleavable complex. To examine the effects of camptothecin on RNA synthesis genome-wide we used Bru-Seq and show that camptothecin treatment affected transcription initiation, elongation, termination, splicing and enhancer activity. Following removal of camptothecin, transcription spread as a wave from the 5-end of genes with no recovery of transcription apparent from RNA polymerases stalled in the body of genes. As a result, camptothecin preferentially inhibited the expression of large genes such as proto-oncogenes, and anti-apoptotic genes while smaller ribosomal protein genes, pro-apoptotic genes and p53 target genes showed relative higher expression. In addition, a set of mitotic regulator genes and histone genes were inhibited in a size-independent manner. Cockayne syndrome group B fibroblasts showed a very similar RNA synthesis recovery profile to normal fibroblasts suggesting that transcription-coupled repair is not involved in the repair of transcription-blocking TOP1 lesions. These findings of the effects of camptothecin on transcription have important implications for its anti-cancer activities and may aid in the design of improved combinatorial treatments involving Top1 poisons. SOURCE: Mats Ljungman (tenbroek@med.umich.edu) - University of Michigan