Concentration of antineoplastic agents into spatial compartments influences activity Many mysteries remain about the eukaryotic nucleus. In the past decade, much has been discovered anew about the three-dimensional (3D) organization… Click to show full abstract
Concentration of antineoplastic agents into spatial compartments influences activity Many mysteries remain about the eukaryotic nucleus. In the past decade, much has been discovered anew about the three-dimensional (3D) organization of the nucleus and the dynamic interactions therein that influence cellular function. Studies have uncovered the critical roles that topologic structure, histone modifications, and DNA modifications play in regulating transcription. By contrast, the understanding of interactions among proteins, RNA, and chromatin in macromolecular assemblies is less developed. These condensates are the molecular basis for discrete nuclear spatial organization of active and repressive chromatin as well as distinct nuclear structures such as the nucleolus (1, 2). On page 1386 of this issue, Klein et al. (3) begin to dissect the functional relevance of nuclear condensates in regulating the distribution and activity of fluorescent-labeled antineoplastic agents with specific nuclear localization profiles. This finding could have wide-ranging implications for the understanding of pharmacologic mechanisms and has substantive consequences for therapeutic development, drug delivery, and target engagement.
               
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