DNA intercalators, actinomycin D and Adriamycin possess anti-cancer activity through inhibition of DNA topoisomerase II. It is reported that histones are released from chromatin by DNA intercalators. In this study, we assessed the effects of released histones on gene expression in an artificial wound healing system using cultured human keratinocyte cells HaCaT. Actinomycin D or Adriamycin was temporarily added to the medium from 5 minutes prior to the artificial wounding until the time point of 25 minutes after the wounding, and cells were cultured for a total of 6 hours after the wounding. Total RNAs were isolated both from hole cells (transcriptome) and polysomal fractions (translatome) and used in differential gene expression analysis by DNA microarray. The DNA microarray analysis revealed that actinomycin D and Adriamycin downregulated the ribosome loading to mRNAs of histone and centromere-related genes. Proteins of these genes were detected immunohistochemically in cytosolic granule by a confocal fluorescence microscopy. These results suggest that actinomycin D and adriamycin are able of exerting a coordinated translational control of the expression of histones and centromere-related genes.
Abstracts of papers presented at the 2016 meeting on TRANSLATIONAL CONTROL, p144
