Transcriptional effects of the potent enediyne anti-cancer agent Calicheamicin gamma(I)(1).
We have investigated the mode of action of calicheamicin in living cells by using oligonucleotide microarrays to monitor its effects on gene expression across the entire yeast genome. Transcriptional effects were observed as early as 2 min into drug exposure. Among these effects were the upregulation of two nuclear proteins encoding a Y'-helicase (a subtelomerically encoded protein whose function is to maintain telomeres) and a suppressor of rpc10 and rpb40 mutations (both rpc10 and rpb40 encode RNA polymerase subunits). With longer calicheamicin exposure, genes involved in chromatin arrangement, DNA repair and/or oxidative damage, DNA synthesis and cell cycle checkpoint control as well as other nuclear proteins were all differentially expressed. Additionally, ribosomal proteins and a variety of metabolic, biosynthetic, and stress response genes were also altered in their expression.
Watanabe
Coran M H
CM
Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA.
Supekova
Lubica
L
Schultz
Peter G
PG
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D004249:DNA Damage; D053281:Enediynes; D015966:Gene Expression Regulation, Fungal; D009687:Nuclear Proteins / Q000187:drug effects / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D014158:Transcription, Genetic
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D053281:Enediynes; D009687:Nuclear Proteins; C055955:calicheamicin gamma(1)I