peripheral membrane proteins. The most important are lamina associated polypeptides 1 and 2 (LAP1, LAP2), emerin, lamin B-receptor (LBR), otefin and MAN1. Due to their positioning within or their association with the inner membrane, they mediate the attachment of the nuclear lamina to the nuclear envelope. Role and interaction aspects The nuclear lamina is assembled by interactions of two lamin polypeptides in which the α-helical regions are wound around each other to form a two stranded α-helical coiled-coil structure, followed by a head-to-tail association of the multiple dimers. The linearly elongated polymer is extended laterally by a side-by-side association of polymers, resulting in a 2D structure underlying the nuclear envelope. Next to providing mechanical support to the nucleus, the nuclear lamina plays an essential role in chromatin organization, cell cycle regulation, DNA replication, DNA repair, cell differentiation and apoptosis. Chromatin organization The non-random organization of the genome strongly suggests that the nuclear lamina plays a role in chromatin organization. It has been shown that lamin polypeptides have an affinity for binding chromatin through their α-helical (rod like) domains at specific DNA sequences called matrix attachment regions (MAR). A MAR has a length of approximately 300–1000 bp and has a high A/T content. Lamin A and B can also bind core histones through a sequence element in their tail domain. Chromatin that interacts with lamina forms lamina-associated domains (LADs). The average length of human LADs is 0.1–10 MBp. LADs are flanked by CTCF-binding sites. Cell cycle regulation At the onset of mitosis (prophase, prometaphase), the cellular machinery is engaged in the disassembly of various cellular components including structures such as the nuclear envelope, the nuclear lamina and the nuclear pore complexes. This nuclear breakdown is necessary to allow the mitotic spindle to interact with the (condensed) chromosomes and to bind them at their kinetochores. These different disassembly events are initiated by the cyclin B/Cdk1 protein kinase complex (MPF). Once this complex is activated, the cell is forced into mitosis, by the subsequent activation and regulation of other protein kinases or by direct phosphorylation of structural proteins involved in this cellular reorganisation. After phosphorylation by cyclin B/Cdk1, the nuclear lamina depolymerises and B-type lamins stay associated with the fragments of the nuclear envelope whereas A-type lamins remain completely soluble throughout the remainder of the mitotic phase. The importance of the nuclear lamina breakdown at this stage is underlined by experiments where inhibition