Bruce A. Fenderson

APOPTOSIS IN HEALTH AND DISEASE: CLINICAL AND THERAPEUTIC ASPECTS

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NUCLEAR ORGANIZATION IN DEVELOPMENT AND DISEASE

The cell nucleus is surrounded by a complex membranous envelope which separates the nucleoplasm from the cytoplasm. Unlike the cytoplasm, the nucleoplasm is not subdivided into membrane-bound compartments, which allows for the e⁄cient segregation of a wide range of complex metabolic activities. In the absence of such membrane compartmentalization, the nucleus is faced with the daunting task of e⁄ciently segregating and interconnecting an enormous array of critically important functions. These include the assembly of the large multi-component complexes or ‘factories’ involved in DNA replication and transcription. These structures are dynamic as they are assembled and disassembled both spatially and temporally at di¡erent times, implying the existence of an infrastructure or nucleoskeleton responsible for establishing and maintaining a complex nuclear architecture. There is increasing evidence that the nuclear lamins are essential elements of this nuclear infrastructure, and that their proper assembly and organization are required for numerous essential nuclear functions. Our goal has been to determine the roles of the nuclear lamins in vital nuclear processes including DNA replication and transcription. The hypothesis directing our investigations is that the lamins form a 3D network that courses throughout the nucleoplasm providing an infrastructure for the assembly and distribution of numerous multicomponent complexes involved in a wide range of nuclear functions. 2005 Nuclear organization in development and disease. Wiley, Chichester (Novartis Foundation Symposium 264) p 3^21 The nuclear lamins are ¢lamentous proteins which comprise the major structural components of the nuclear lamina. Electron microscopy has revealed that the lamina is an electron-dense layer immediately subjacent to the inner nuclear envelope membrane. The lamina forms a molecular interface between the inner membrane and nucleoplasmic structures such as chromatin. Lamins are also found distributed throughout the nucleoplasm where they appear in several organizational states, including distinct foci and/or relatively uniform ‘veils’ that appear to course throughout the nucleoplasm (Fig. 1; Moir et al 2000a, Liu et al 2000).