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About This Issue…

The nucleus has been recognized as a quintessential feature of the cell for well over a hundred years, but throughout the century subsequent to Friedrich Miescher’s 1869 discovery of “nuclein,” or nucleic acid, the questions that most intrigued biologists concerned the nature of the macromolecules that the nucleus contains. Certainly the attention given to the nucleic acids was warranted. After all, it had been established by the turn of the century that the nucleus determined inheritance, and much of the chromosome behavior that we now know as mitosis and meiosis had been described. But the nucleus as a cellular organelle, defined primarily by an “envelope” with holes in it, hardly seemed spectacular. Indeed, its very existence was relegated to a period of cellular metabolism known as interphase, which microscopists had to tolerate until the nuclear envelope would finally disappear and the chromosomes would resume the more fascinating aspects of mitosis. In the last quarter century, as additional details of gene structure, regulation, and expression have been elaborated, new questions have arisen so as to shift attention back to the interphase nucleus. A major conceptual challenge, for example, has been to understand the mechanisms whereby a genome’s worth of DNA, which in some instances can be extended to the order of a meter in length, is condensed into a nucleus that measures on the order of a few micrometers in diameter. Beyond the specific association of genomic DNA with histones so as to produce the 10and 30-nm fibers first described in the 1970s, it is still not fully clear how nuclear DNA can be made so compact. On top of the problem of DNA condensation per se are the equally formidable challenges of understanding (1) how The Nucleocytoplasmic Continuum: Pushing the (Nuclear) Envelope