Nuclear lamina

The nuclear lamina is a dense (~30 to 100 nm thick) fibrillar network inside the nucleus of eukaryote cells.

Besides providing mechanical support, the nuclear lamina regulates important cellular events such as DNA replication and cell division.

In the amino acid sequence of a nuclear lamin, there are also two phosphoacceptor sites present, flanking the central rod domain.

A phosphorylation event at the onset of mitosis leads to a conformational change which causes the disassembly of the nuclear lamina.

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).

The importance of the nuclear lamina breakdown at this stage is underlined by experiments where inhibition of the disassembly event leads to a complete cell cycle arrest.

The presence of lamins in embryonic development is readily observed in various model organisms such as Xenopus laevis, the chick and mammals.

Various experiments show that the nuclear lamina plays a part in the elongation phase of DNA replication.

Repair of DNA double-strand breaks can occur by either of two processes, non-homologous end joining (NHEJ) or homologous recombination (HR).

A-type lamins promote genetic stability by maintaining levels of proteins that have key roles in NHEJ and HR.

[6] Apoptosis is a form of programmed cell death that is critical in tissue homeostasis, and in defending the organism against invasive entry of pathogens.

This proteolytic activity is performed by members of the caspase-protein family who cleave the lamins after aspartic acid (Asp) residues.

Confocal microscopic analysis of dermal fibroblasts in primary culture from a control (a and b) and the subject with progeria (c and d). Labelling was performed with anti- lamin A/C antibodies. Irregularly shaped nuclear envelopes are seen in many of the progeria fibroblasts .
Structure and function of the nuclear lamina. The nuclear lamina lies on the inner surface of the inner nuclear membrane (INM), where it serves to maintain nuclear stability, organize chromatin and bind nuclear pore complexes (NPCs) and a steadily growing list of nuclear envelope proteins (purple) and transcription factors (pink). Nuclear envelope proteins that are bound to the lamina include nesprin, emerin, lamina-associated proteins 1 and 2 (LAP1 and LAP2), the lamin B receptor (LBR) and MAN1. Transcription factors that bind to the lamina include the retinoblastoma transcriptional regulator (RB), germ cell-less (GCL), sterol response element binding protein (SREBP1), FOS and MOK2. Barrier to autointegration factor (BAF) is a chromatin-associated protein that also binds to the nuclear lamina and several of the aforementioned nuclear envelope proteins. Heterochromatin protein 1 (HP1) binds both chromatin and the LBR. ONM, outer nuclear membrane. [ 2 ]