@article{11100, abstract = {Eukaryotic cell function depends on the physical separation of nucleoplasmic and cytoplasmic components by the nuclear envelope (NE). Molecular communication between the two compartments involves active, signal-mediated trafficking, a function that is exclusively performed by nuclear pore complexes (NPCs). The individual NPC components and the mechanisms that are involved in nuclear trafficking are well documented and have become textbook knowledge. However, in addition to their roles as nuclear gatekeepers, NPC components-nucleoporins-have been shown to have critical roles in chromatin organization and gene regulation. These findings have sparked new enthusiasm to study the roles of this multiprotein complex in nuclear organization and explore novel functions that in some cases appear to go beyond a role in transport. Here, we discuss our present view of NPC biogenesis, which is tightly linked to proper cell cycle progression and cell differentiation. In addition, we summarize new data suggesting that NPCs represent dynamic hubs for the integration of gene regulation and nuclear transport processes.}, author = {Capelson, M. and Doucet, C. and HETZER, Martin W}, isbn = {9781936113071}, issn = {0091-7451}, journal = {Cold Spring Harbor Symposia on Quantitative Biology}, keywords = {Genetics, Molecular Biology, Biochemistry}, pages = {585--597}, publisher = {Cold Spring Harbor Laboratory Press}, title = {{Nuclear pore complexes: Guardians of the nuclear genome}}, doi = {10.1101/sqb.2010.75.059}, volume = {75}, year = {2011}, } @article{12199, abstract = {The four microsporangia of the flowering plant anther develop from archesporial cells in the L2 of the primordium. Within each microsporangium, developing microsporocytes are surrounded by concentric monolayers of tapetal, middle layer and endothecial cells. How this intricate array of tissues, each containing relatively few cells, is established in an organ possessing no formal meristems is poorly understood. We describe here the pivotal role of the LRR receptor kinase EXCESS MICROSPOROCYTES 1 (EMS1) in forming the monolayer of tapetal nurse cells in Arabidopsis. Unusually for plants, tapetal cells are specified very early in development, and are subsequently stimulated to proliferate by a receptor-like kinase (RLK) complex that includes EMS1. Mutations in members of this EMS1 signalling complex and its putative ligand result in male-sterile plants in which tapetal initials fail to proliferate. Surprisingly, these cells continue to develop, isolated at the locular periphery. Mutant and wild-type microsporangia expand at similar rates and the ‘tapetal’ space at the periphery of mutant locules becomes occupied by microsporocytes. However, induction of late expression of EMS1 in the few tapetal initials in ems1 plants results in their proliferation to generate a functional tapetum, and this proliferation suppresses microsporocyte number. Our experiments also show that integrity of the tapetal monolayer is crucial for the maintenance of the polarity of divisions within it. This unexpected autonomy of the tapetal ‘lineage’ is discussed in the context of tissue development in complex plant organs, where constancy in size, shape and cell number is crucial.}, author = {Feng, Xiaoqi and Dickinson, Hugh G.}, issn = {1477-9129}, journal = {Development}, keywords = {Developmental Biology, Molecular Biology, Anther Tapetum, Arabidopsis, Cell Fate Establishment, EMS1, Reproductive Cell Lineage}, number = {14}, pages = {2409--2416}, publisher = {The Company of Biologists}, title = {{Tapetal cell fate, lineage and proliferation in the Arabidopsis anther}}, doi = {10.1242/dev.049320}, volume = {137}, year = {2010}, } @article{8473, abstract = {β2-microglobulin (β2m), the light chain of class I major histocompatibility complex, is responsible for the dialysis-related amyloidosis and, in patients undergoing long term dialysis, the full-length and chemically unmodified β2m converts into amyloid fibrils. The protein, belonging to the immunoglobulin superfamily, in common to other members of this family, experiences during its folding a long-lived intermediate associated to the trans-to-cis isomerization of Pro-32 that has been addressed as the precursor of the amyloid fibril formation. In this respect, previous studies on the W60G β2m mutant, showing that the lack of Trp-60 prevents fibril formation in mild aggregating condition, prompted us to reinvestigate the refolding kinetics of wild type and W60G β2m at atomic resolution by real-time NMR. The analysis, conducted at ambient temperature by the band selective flip angle short transient real-time two-dimensional NMR techniques and probing the β2m states every 15 s, revealed a more complex folding energy landscape than previously reported for wild type β2m, involving more than a single intermediate species, and shedding new light into the fibrillogenic pathway. Moreover, a significant difference in the kinetic scheme previously characterized by optical spectroscopic methods was discovered for the W60G β2m mutant.}, author = {Corazza, Alessandra and Rennella, Enrico and Schanda, Paul and Mimmi, Maria Chiara and Cutuil, Thomas and Raimondi, Sara and Giorgetti, Sofia and Fogolari, Federico and Viglino, Paolo and Frydman, Lucio and Gal, Maayan and Bellotti, Vittorio and Brutscher, Bernhard and Esposito, Gennaro}, issn = {0021-9258}, journal = {Journal of Biological Chemistry}, keywords = {Cell Biology, Biochemistry, Molecular Biology}, number = {8}, pages = {5827--5835}, publisher = {American Society for Biochemistry & Molecular Biology}, title = {{Native-unlike long-lived intermediates along the folding pathway of the amyloidogenic protein β2-Microglobulin revealed by real-time two-dimensional NMR}}, doi = {10.1074/jbc.m109.061168}, volume = {285}, year = {2010}, } @article{11097, abstract = {The nuclear envelope (NE) is a highly regulated membrane barrier that separates the nucleus from the cytoplasm in eukaryotic cells. It contains a large number of different proteins that have been implicated in chromatin organization and gene regulation. Although the nuclear membrane enables complex levels of gene expression, it also poses a challenge when it comes to cell division. To allow access of the mitotic spindle to chromatin, the nucleus of metazoans must completely disassemble during mitosis, generating the need to re-establish the nuclear compartment at the end of each cell division. Here, I summarize our current understanding of the dynamic remodeling of the NE during the cell cycle.}, author = {HETZER, Martin W}, issn = {1943-0264}, journal = {Cold Spring Harbor Perspectives in Biology}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {3}, pages = {a000539--a000539}, publisher = {Cold Spring Harbor Laboratory}, title = {{The nuclear envelope}}, doi = {10.1101/cshperspect.a000539}, volume = {2}, year = {2010}, } @article{11098, author = {HETZER, Martin W}, issn = {1945-4589}, journal = {Aging}, keywords = {Cell Biology, Aging}, number = {2}, pages = {74--75}, publisher = {Impact Journals}, title = {{The role of the nuclear pore complex in aging of post-mitotic cells}}, doi = {10.18632/aging.100125}, volume = {2}, year = {2010}, } @article{11101, abstract = {In metazoa, nuclear pore complexes (NPCs) assemble from disassembled precursors into a reforming nuclear envelope (NE) at the end of mitosis and into growing intact NEs during interphase. Here, we show via RNAi-mediated knockdown that ELYS, a nucleoporin critical for the recruitment of the essential Nup107/160 complex to chromatin, is required for NPC assembly at the end of mitosis but not during interphase. Conversely, the transmembrane nucleoporin POM121 is critical for the incorporation of the Nup107/160 complex into new assembly sites specifically during interphase. Strikingly, recruitment of the Nup107/160 complex to an intact NE involves a membrane curvature-sensing domain of its constituent Nup133, which is not required for postmitotic NPC formation. Our results suggest that in organisms with open mitosis, NPCs assemble via two distinct mechanisms to accommodate cell cycle-dependent differences in NE topology.}, author = {Doucet, Christine M. and Talamas, Jessica A. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {6}, pages = {1030--1041}, publisher = {Elsevier}, title = {{Cell cycle-dependent differences in nuclear pore complex assembly in metazoa}}, doi = {10.1016/j.cell.2010.04.036}, volume = {141}, year = {2010}, } @article{11102, abstract = {Nuclear pore complexes have recently been shown to play roles in gene activation; however their potential involvement in metazoan transcription remains unclear. Here we show that the nucleoporins Sec13, Nup98, and Nup88, as well as a group of FG-repeat nucleoporins, bind to the Drosophila genome at functionally distinct loci that often do not represent nuclear envelope contact sites. Whereas Nup88 localizes to silent loci, Sec13, Nup98, and a subset of FG-repeat nucleoporins bind to developmentally regulated genes undergoing transcription induction. Strikingly, RNAi-mediated knockdown of intranuclear Sec13 and Nup98 specifically inhibits transcription of their target genes and prevents efficient reactivation of transcription after heat shock, suggesting an essential role of NPC components in regulating complex gene expression programs of multicellular organisms.}, author = {Capelson, Maya and Liang, Yun and Schulte, Roberta and Mair, William and Wagner, Ulrich and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {3}, pages = {372--383}, publisher = {Elsevier}, title = {{Chromatin-bound nuclear pore components regulate gene expression in higher eukaryotes}}, doi = {10.1016/j.cell.2009.12.054}, volume = {140}, year = {2010}, } @article{11103, abstract = {Over the last decade, the nuclear envelope (NE) has emerged as a key component in the organization and function of the nuclear genome. As many as 100 different proteins are thought to specifically localize to this double membrane that separates the cytoplasm and the nucleoplasm of eukaryotic cells. Selective portals through the NE are formed at sites where the inner and outer nuclear membranes are fused, and the coincident assembly of ∼30 proteins into nuclear pore complexes occurs. These nuclear pore complexes are essential for the control of nucleocytoplasmic exchange. Many of the NE and nuclear pore proteins are thought to play crucial roles in gene regulation and thus are increasingly linked to human diseases.}, author = {HETZER, Martin W and Wente, Susan R.}, issn = {1534-5807}, journal = {Developmental Cell}, keywords = {Developmental Biology, Cell Biology, General Biochemistry, Genetics and Molecular Biology, Molecular Biology}, number = {5}, pages = {606--616}, publisher = {Elsevier}, title = {{Border control at the nucleus: Biogenesis and organization of the nuclear membrane and pore complexes}}, doi = {10.1016/j.devcel.2009.10.007}, volume = {17}, year = {2009}, } @article{11105, abstract = {Nuclear-pore complexes (NPCs) are large protein channels that span the nuclear envelope (NE), which is a double membrane that encloses the nuclear genome of eukaryotes. Each of the typically 2,000–4,000 pores in the NE of vertebrate cells is composed of multiple copies of 30 different proteins known as nucleoporins. The evolutionarily conserved NPC proteins have the well-characterized function of mediating the transport of molecules between the nucleoplasm and the cytoplasm. Mutations in nucleoporins are often linked to specific developmental defects and disease, and the resulting phenotypes are usually interpreted as the consequences of perturbed nuclear transport activity. However, recent evidence suggests that NPCs have additional functions in chromatin organization and gene regulation, some of which might be independent of nuclear transport. Here, we review the transport-dependent and transport-independent roles of NPCs in the regulation of nuclear function and gene expression.}, author = {Capelson, Maya and HETZER, Martin W}, issn = {1469-3178}, journal = {EMBO reports}, keywords = {Genetics, Molecular Biology, Biochemistry}, number = {7}, pages = {697--705}, publisher = {EMBO}, title = {{The role of nuclear pores in gene regulation, development and disease}}, doi = {10.1038/embor.2009.147}, volume = {10}, year = {2009}, } @article{11106, abstract = {Formation of the nuclear envelope (NE) around segregated chromosomes occurs by the reshaping of the endoplasmic reticulum (ER), a reservoir for disassembled nuclear membrane components during mitosis. In this study, we show that inner nuclear membrane proteins such as lamin B receptor (LBR), MAN1, Lap2β, and the trans-membrane nucleoporins Ndc1 and POM121 drive the spreading of ER membranes into the emerging NE via their capacity to bind chromatin in a collaborative manner. Despite their redundant functions, decreasing the levels of any of these trans-membrane proteins by RNAi-mediated knockdown delayed NE formation, whereas increasing the levels of any of them had the opposite effect. Furthermore, acceleration of NE formation interferes with chromosome separation during mitosis, indicating that the time frame over which chromatin becomes membrane enclosed is physiologically relevant and regulated. These data suggest that functionally distinct classes of chromatin-interacting membrane proteins, which are present at nonsaturating levels, collaborate to rapidly reestablish the nuclear compartment at the end of mitosis.}, author = {Anderson, Daniel J. and Vargas, Jesse D. and Hsiao, Joshua P. and HETZER, Martin W}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {2}, pages = {183--191}, publisher = {Rockefeller University Press}, title = {{Recruitment of functionally distinct membrane proteins to chromatin mediates nuclear envelope formation in vivo}}, doi = {10.1083/jcb.200901106}, volume = {186}, year = {2009}, } @article{11107, abstract = {Nucleocytoplasmic transport occurs exclusively through nuclear pore complexes (NPCs) embedded in pores formed by inner and outer nuclear membrane fusion. The mechanism for de novo pore and NPC biogenesis remains unclear. Reticulons (RTNs) and Yop1/DP1 are conserved membrane protein families required to form and maintain the tubular endoplasmic reticulum (ER) and the postmitotic nuclear envelope. In this study, we report that members of the RTN and Yop1/DP1 families are required for nuclear pore formation. Analysis of Saccharomyces cerevisiae prp20-G282S and nup133Δ NPC assembly mutants revealed perturbations in Rtn1–green fluorescent protein (GFP) and Yop1-GFP ER distribution and colocalization to NPC clusters. Combined deletion of RTN1 and YOP1 resulted in NPC clustering, nuclear import defects, and synthetic lethality with the additional absence of Pom34, Pom152, and Nup84 subcomplex members. We tested for a direct role in NPC biogenesis using Xenopus laevis in vitro assays and found that anti-Rtn4a antibodies specifically inhibited de novo nuclear pore formation. We hypothesize that these ER membrane–bending proteins mediate early NPC assembly steps.}, author = {Dawson, T. Renee and Lazarus, Michelle D. and HETZER, Martin W and Wente, Susan R.}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {5}, pages = {659--675}, publisher = {Rockefeller University Press}, title = {{ER membrane–bending proteins are necessary for de novo nuclear pore formation}}, doi = {10.1083/jcb.200806174}, volume = {184}, year = {2009}, } @article{11108, abstract = {In dividing cells, nuclear pore complexes (NPCs) disassemble during mitosis and reassemble into the newly forming nuclei. However, the fate of nuclear pores in postmitotic cells is unknown. Here, we show that NPCs, unlike other nuclear structures, do not turn over in differentiated cells. While a subset of NPC components, like Nup153 and Nup50, are continuously exchanged, scaffold nucleoporins, like the Nup107/160 complex, are extremely long-lived and remain incorporated in the nuclear membrane during the entire cellular life span. Besides the lack of nucleoporin expression and NPC turnover, we discovered an age-related deterioration of NPCs, leading to an increase in nuclear permeability and the leaking of cytoplasmic proteins into the nucleus. Our finding that nuclear “leakiness” is dramatically accelerated during aging and that a subset of nucleoporins is oxidatively damaged in old cells suggests that the accumulation of damage at the NPC might be a crucial aging event.}, author = {D'Angelo, Maximiliano A. and Raices, Marcela and Panowski, Siler H. and HETZER, Martin W}, issn = {0092-8674}, journal = {Cell}, keywords = {General Biochemistry, Genetics and Molecular Biology}, number = {2}, pages = {284--295}, publisher = {Elsevier}, title = {{Age-dependent deterioration of nuclear pore complexes causes a loss of nuclear integrity in postmitotic cells}}, doi = {10.1016/j.cell.2008.11.037}, volume = {136}, year = {2009}, } @article{8480, abstract = {The KIX domain of the transcription co-activator CBP is a three-helix bundle protein that folds via rapid accumulation of an intermediate state, followed by a slower folding phase. Recent NMR relaxation dispersion studies revealed the presence of a low-populated (excited) state of KIX that exists in equilibrium with the natively folded form under non-denaturing conditions, and likely represents the equilibrium analog of the folding intermediate. Here, we combine amide hydrogen/deuterium exchange measurements using rapid NMR data acquisition techniques with backbone 15N and 13C relaxation dispersion experiments to further investigate the equilibrium folding of the KIX domain. Residual structure within the folding intermediate is detected by both methods, and their combination enables reliable quantification of the amount of persistent residual structure. Three well-defined folding subunits are found, which display variable stability and correspond closely to the individual helices in the native state. While two of the three helices (α2 and α3) are partially formed in the folding intermediate (to ∼ 50% and ∼ 80%, respectively, at 20 °C), the third helix is disordered. The observed helical content within the excited state exceeds the helical propensities predicted for the corresponding peptide regions, suggesting that the two helices are weakly mutually stabilized, while methyl 13C relaxation dispersion data indicate that a defined packing arrangement is unlikely. Temperature-dependent experiments reveal that the largest enthalpy and entropy changes along the folding reaction occur during the final transition from the intermediate to the native state. Our experimental data are consistent with a folding mechanism where helices α2 and α3 form rapidly, although to different extents, while helix α1 consolidates only as folding proceeds to complete the native state-structure.}, author = {Schanda, Paul and Brutscher, Bernhard and Konrat, Robert and Tollinger, Martin}, issn = {0022-2836}, journal = {Journal of Molecular Biology}, keywords = {Molecular Biology}, number = {4}, pages = {726--741}, publisher = {Elsevier}, title = {{Folding of the KIX domain: Characterization of the equilibrium analog of a folding intermediate using 15N/13C relaxation dispersion and fast 1H/2H amide exchange NMR spectroscopy}}, doi = {10.1016/j.jmb.2008.05.040}, volume = {380}, year = {2008}, } @article{8481, abstract = {The copK gene is localized on the pMOL30 plasmid of Cupriavidus metallidurans CH34 within the complex cop cluster of genes, for which 21 genes have been identified. The expression of the corresponding periplasmic CopK protein is strongly upregulated in the presence of copper, leading to a high periplasmic accumulation. The structure and metal-binding properties of CopK were investigated by NMR and mass spectrometry. The protein is dimeric in the apo state with a dissociation constant in the range of 10- 5 M estimated from analytical ultracentrifugation. Mass spectrometry revealed that CopK has two high-affinity Cu(I)-binding sites per monomer with different Cu(I) affinities. Binding of Cu(II) was observed but appeared to be non-specific. The solution structure of apo-CopK revealed an all-β fold formed of two β-sheets in perpendicular orientation with an unstructured C-terminal tail. The dimer interface is formed by the surface of the C-terminal β-sheet. Binding of the first Cu(I)-ion induces a major structural modification involving dissociation of the dimeric apo-protein. Backbone chemical shifts determined for the 1Cu(I)-bound form confirm the conservation of the N-terminal β-sheet, while the last strand of the C-terminal sheet appears in slow conformational exchange. We hypothesize that the partial disruption of the C-terminal β-sheet is related to dimer dissociation. NH-exchange data acquired on the apo-protein are consistent with a lower thermodynamic stability of the C-terminal sheet. CopK contains seven methionine residues, five of which appear highly conserved. Chemical shift data suggest implication of two or three methionines (Met54, Met38, Met28) in the first Cu(I) site. Addition of a second Cu(I) ion further increases protein plasticity. Comparison of the structural and metal-binding properties of CopK with other periplasmic copper-binding proteins reveals two conserved features within these functionally related proteins: the all-β fold and the methionine-rich Cu(I)-binding site.}, author = {Bersch, Beate and Favier, Adrien and Schanda, Paul and van Aelst, Sébastien and Vallaeys, Tatiana and Covès, Jacques and Mergeay, Max and Wattiez, Ruddy}, issn = {0022-2836}, journal = {Journal of Molecular Biology}, keywords = {Molecular Biology}, number = {2}, pages = {386--403}, publisher = {Elsevier}, title = {{Molecular structure and metal-binding properties of the periplasmic CopK protein expressed in Cupriavidus metallidurans CH34 during copper challenge}}, doi = {10.1016/j.jmb.2008.05.017}, volume = {380}, year = {2008}, } @article{11109, abstract = {The nuclear envelope (NE) provides a selective barrier between the nuclear interior and the cytoplasm and constitutes a central component of intracellular architecture. During mitosis in metazoa, the NE breaks down leading to the complete mixing of the nuclear content with the cytosol. Interestingly, many NE components actively participate in mitotic progression. After chromosome segregation, the NE is reassembled around decondensing chromatin and the nuclear compartment is reestablished in the daughter cells. Here, we summarize recent progress in deciphering the molecular mechanisms underlying NE dynamics during cell division.}, author = {Kutay, Ulrike and HETZER, Martin W}, issn = {0955-0674}, journal = {Current Opinion in Cell Biology}, keywords = {Cell Biology}, number = {6}, pages = {669--677}, publisher = {Elsevier}, title = {{Reorganization of the nuclear envelope during open mitosis}}, doi = {10.1016/j.ceb.2008.09.010}, volume = {20}, year = {2008}, } @article{11110, abstract = {Nuclear pore complexes are large aqueous channels that penetrate the nuclear envelope, thereby connecting the nuclear interior with the cytoplasm. Until recently, these macromolecular complexes were viewed as static structures, the only function of which was to control the molecular trafficking between the two compartments. It has now become evident that this simplistic scenario is inaccurate and that nuclear pore complexes are highly dynamic multiprotein assemblies involved in diverse cellular processes ranging from the organization of the cytoskeleton to gene expression. In this review, we discuss the most recent developments in the nuclear-pore-complex field, focusing on the assembly, disassembly, maintenance and function of this macromolecular structure.}, author = {D’Angelo, Maximiliano A. and HETZER, Martin W}, issn = {0962-8924}, journal = {Trends in Cell Biology}, keywords = {Cell Biology}, number = {10}, pages = {456--466}, publisher = {Elsevier}, title = {{Structure, dynamics and function of nuclear pore complexes}}, doi = {10.1016/j.tcb.2008.07.009}, volume = {18}, year = {2008}, } @article{11111, abstract = {During mitosis in metazoans, segregated chromosomes become enclosed by the nuclear envelope (NE), a double membrane that is continuous with the endoplasmic reticulum (ER). Recent in vitro data suggest that NE formation occurs by chromatin-mediated reorganization of the tubular ER; however, the basic principles of such a membrane-reshaping process remain uncharacterized. Here, we present a quantitative analysis of nuclear membrane assembly in mammalian cells using time-lapse microscopy. From the initial recruitment of ER tubules to chromatin, the formation of a membrane-enclosed, transport-competent nucleus occurs within ∼12 min. Overexpression of the ER tubule-forming proteins reticulon 3, reticulon 4, and DP1 inhibits NE formation and nuclear expansion, whereas their knockdown accelerates nuclear assembly. This suggests that the transition from membrane tubules to sheets is rate-limiting for nuclear assembly. Our results provide evidence that ER-shaping proteins are directly involved in the reconstruction of the nuclear compartment and that morphological restructuring of the ER is the principal mechanism of NE formation in vivo.}, author = {Anderson, Daniel J. and HETZER, Martin W}, issn = {1540-8140}, journal = {Journal of Cell Biology}, keywords = {Cell Biology}, number = {5}, pages = {911--924}, publisher = {Rockefeller University Press}, title = {{Reshaping of the endoplasmic reticulum limits the rate for nuclear envelope formation}}, doi = {10.1083/jcb.200805140}, volume = {182}, year = {2008}, } @article{11112, abstract = {The nuclear envelope is a double-layered membrane that encloses the nuclear genome and transcriptional machinery. In dividing cells of metazoa, the nucleus completely disassembles during mitosis, creating the need to re-establish the nuclear compartment at the end of each cell division. Given the crucial role of the nuclear envelope in gene regulation and cellular organization, it is not surprising that its biogenesis and organization have become active research areas. We will review recent insights into nuclear membrane dynamics during the cell cycle.}, author = {Anderson, Daniel J and HETZER, Martin W}, issn = {0955-0674}, journal = {Current Opinion in Cell Biology}, keywords = {Cell Biology}, number = {4}, pages = {386--392}, publisher = {Elsevier}, title = {{The life cycle of the metazoan nuclear envelope}}, doi = {10.1016/j.ceb.2008.03.016}, volume = {20}, year = {2008}, } @article{11113, abstract = {The nuclear envelope (NE), a double membrane enclosing the nucleus of eukaryotic cells, controls the flow of information between the nucleoplasm and the cytoplasm and provides a scaffold for the organization of chromatin and the cytoskeleton. In dividing metazoan cells, the NE breaks down at the onset of mitosis and then reforms around segregated chromosomes to generate the daughter nuclei. Recent data from intact cells and cell-free nuclear assembly systems suggest that the endoplasmic reticulum (ER) is the source of membrane for NE assembly. At the end of mitosis, ER membrane tubules are targeted to chromatin via tubule ends and reorganized into flat nuclear membrane sheets by specific DNA-binding membrane proteins. In contrast to previous models, which proposed vesicle fusion to be the principal mechanism of NE formation, these new studies suggest that the nuclear membrane forms by the chromatin-mediated reshaping of the ER.}, author = {Anderson, Daniel J. and HETZER, Martin W}, issn = {1477-9137}, journal = {Journal of Cell Science}, keywords = {Cell Biology}, number = {2}, pages = {137--142}, publisher = {The Company of Biologists}, title = {{Shaping the endoplasmic reticulum into the nuclear envelope}}, doi = {10.1242/jcs.005777}, volume = {121}, year = {2008}, } @article{11115, abstract = {The formation of the nuclear envelope (NE) around chromatin is a major membrane-remodelling event that occurs during cell division of metazoa. It is unclear whether the nuclear membrane reforms by the fusion of NE fragments or if it re-emerges from an intact tubular network of the endoplasmic reticulum (ER). Here, we show that NE formation and expansion requires a tubular ER network and occurs efficiently in the presence of the membrane fusion inhibitor GTPγS. Chromatin recruitment of membranes, which is initiated by tubule-end binding, followed by the formation, expansion and sealing of flat membrane sheets, is mediated by DNA-binding proteins residing in the ER. Thus, chromatin plays an active role in reshaping of the ER during NE formation.}, author = {Anderson, Daniel J. and HETZER, Martin W}, issn = {1476-4679}, journal = {Nature Cell Biology}, keywords = {Cell Biology}, number = {10}, pages = {1160--1166}, publisher = {Springer Nature}, title = {{Nuclear envelope formation by chromatin-mediated reorganization of the endoplasmic reticulum}}, doi = {10.1038/ncb1636}, volume = {9}, year = {2007}, }