UC San Diego

The nucleus, defined by its enclosing boundary, the nuclear envelope, is the largest organelle in most eukaryotic cells and houses the nuclear genome. It has been implicated in various physiological processes crucial to normal cell function, processes that are often altered in disease. Here we show that the re-establishment of this critical organelle after cellular division is achieved by a co-opting of numerous proteins of the inner nuclear membrane that interact with DNA/chromatin and that each serve distinct interphase functions. That such a large number of proteins and resources are dedicated to the rapid reformation of the nuclear envelope and proper nuclear compartmentalization suggests its critical importance for normal cell function. Subsequently, we show that this barrier function and the integrity of the nuclear envelope is transiently disrupted in human cancer cells, leading to the mislocalization of both nuclear and cytoplasmic proteins. In extreme cases, this loss of integrity leads to a partial loss of cellular compartmentalization, with normally cytoplasmic organelles appearing in the interior of the cell nucleus. These rupture events are transient and recoverable, but the efflux of genomic material from the nucleus during such events suggests potential genomic insult that may contribute to alterations in genetic information and to the transformation process in cancer.