Three-Dimensional Organization of Chromatids by Nuclear Envelope-Associated Structures

Laboratory of Cell Biology, The Rockefeller University Howard Hughes Medical Institute, New York, New York 10065, USA.
Cold Spring Harbor Symposia on Quantitative Biology 11/2010; 75:545-54. DOI: 10.1101/sqb.2010.75.004
Source: PubMed


In evolution, the nuclear envelope (NE) arose from the prokaryotic plasma membrane. NE-associated structures, such as nuclear pore complexes (NPCs), the nuclear lamina, and nuclear envelope junctions (NEJs), have evolved to organize, among other things, chromatids within the three-dimensional space of the nucleus. NEJs represent patches of distinct integral membrane proteins of the outer and inner NE membranes, which, by interacting through conserved domains in the perinuclear space, closely align the two NE membranes. In a nuts-and-bolts configuration, the NEJs are linked to repetitive heterochromatin segments of chromatids on their nuclear side and to cytoskeletal elements on their cytoplasmic side. Cytoskeleton-generated mechanical forces are thereby effectively buffered to allow movement of nuclei in the viscous cytoplasm without disrupting the NE. Moreover, these same mechanical forces could generate distortions within the nucleus to facilitate chromatid fluctuations required for DNA repair, replication, and transcription. NPCs are the only route for bidirectional macromolecular transport between the cytoplasm and the nucleus. They also interact with euchromatin segments of chromatids. Thus far, crystallographic analyses of some nucleoporin contact sites suggest considerable plasticity. This flexibility has likely coevolved to not only buffer the mechanical forces propagated from the NEJs to the network of the more than 500 nucleoporins that make up a single NPC, but also impart fluctuations to NPC conformations for transporting large cargoes.

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    • "Nuclear pore complexes (NPCs) consist of 30 nucleoproteins that mediate bidirectional trafficking across the nuclear envelope (Blobel, 2010; Wälde and Kehlenbach, 2010; Grünwald et al., 2011). In animal cells, the NPCs are nonmotile and evenly distributed (Daigle et al., 2001; Rabut et al., 2004; Dultz and Ellenberg, 2010). "
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