WEAVING A PATTERN FROM DISPARATE THREADS - LAMIN FUNCTION IN NUCLEAR ASSEMBLY AND DNA-REPLICATION

The major residual structure that remains associated with the nuclear envelope following extraction of isolated nuclei or oocyte germinal ve sicles with non-ionic detergents, nucleases and high salt is the lamin a (Fawcett, 1966; Aaronson and Blobel, 1975; Dwyer and Blobel, 1976), The nuclear lamina is composed of intermediate filament proteins, term ed lamins (Gerace and Blobel, 1980; Shelton et al., 1980), which polym erise to farm a basket-weave lattice of fibrils, which covers the enti re inner surface of the nuclear envelope and interlinks nuclear pores (Aebi et al., 1986; Stewart and Whytock, 1988; Goldberg and Alien, 199 2). At mitosis, the nuclear envelope and the lamina both break down to allow chromosome segregation, As a consequence, each structure has to be rebuilt during anaphase and telophase, allowing cells an opportuni ty to reposition chromosomes (Heslop-Harrison and Bennett, 1990) and t o reorganise looped chromatin domains (Franke, 1974; Franke et al., 19 81; Hochstrasser et al., 1986), which may in turn control the use of s ubsets of genes. Because of the position that it occupies, its dynamic s during mitosis and the fact that it is an essential component of pro liferating cells, the lamina has been assigned a number of putative ro les both in nuclear metabolism and in nuclear envelope assembly (Burke and Gerace, 1986; Nigg, 1989). However, to date there is little clear cut evidence that satisfactorily explains the function of the lamina in relation to its structure, In this Commentary we will describe some of the recent work that addresses this problem and attempt to provide a unified model for the role of lamins in nuclear envelope assembly a nd for the lamina in the initiation of DNA replication.