Dynamic as well as stable protein interactions contribute to genome function and maintenance

The cell nucleus is responsible for the storage, expression, propagation, and maintenance of the genetic material it contains. Highly organized macromolecular complexes are required for these processes to occur faithfully in an extremely crowded nuclear environment. In addition to chromosome territories, the nucleus is characterized by the presence of nuclear substructures, such as the nuclear envelope, the nucleolus, and other nuclear bodies. Other smaller structural entities assemble on chromatin in response to required functions including RNA transcription, DNA replication, and DNA repair. Experiments in living cells over the last decade have revealed that many DNA binding proteins have very short residence times on chromatin. These observations have led to a model in which the assembly of nuclear macromolecular complexes is based on the transient binding of their components. While indeed most nuclear proteins are highly dynamic, we found after an extensive survey of the FRAP literature that an important subset of nuclear proteins shows either very slow turnover or complete immobility. These examples provide compelling evidence for the establishment of stable protein complexes in the nucleus over significant fractions of the cell cycle. Stable interactions in the nucleus may, therefore, contribute to the maintenance of genome integrity. Based on our compilation of FRAP data, we propose an extension of the existing model for nuclear organization which now incorporates stable interactions. Our new "induced stability" model suggests that self-organization, self-assembly, and assisted assembly contribute to nuclear architecture and function.