GO:0031468 nuclear membrane reassembly: Components, Assembly and Research Methods, Genes, Functions and Research Methods
Research-grade guide for scientists and biopharma professionals
Key Takeaways
• GO:0031468 nuclear membrane reassembly is the biological process by which the nuclear membranes reform after their breakdown during a normal process such as mitosis.
• Reassembly requires dephosphorylation of mitotic phosphoproteins, reformation of the nuclear envelope, and re-establishment of nuclear pore complexes.
• Key molecular players include emerin, VCP/p97, VCPIP1, and proteins involved in DNA repair such as TMEJ factors.
• Defects in nuclear membrane reassembly are linked to replication stress, genome instability, and diseases such as cancer and laminopathies.
• CRISPR-based models (knockout, point mutation, knock-in, overexpression) enable causal testing of genes implicated in nuclear membrane reassembly.
• Studying this process benefits from imaging, proteomics, and functional genomics, with QuickGO providing the authoritative definition and ontology context.
Description
Nuclear membrane reassembly (GO:0031468) is the biological process that reforms the nuclear membranes after their disassembly during a normal cellular event, most prominently mitosis. This process is essential for restoring the nuclear compartment, protecting the genome, and re-establishing nucleocytoplasmic transport. Research into nuclear membrane reassembly has revealed a tightly coordinated sequence of membrane reformation, chromatin decondensation, and nuclear pore complex reassembly. Understanding this process is critical because its failure can lead to replication stress, DNA damage, and diseases ranging from cancer to laminopathies. The QuickGO definition provides a precise ontology anchor for annotating genes and proteins involved in this process. This article synthesizes published findings on the mechanisms, key genes, disease links, and research methods for studying nuclear membrane reassembly.
nuclear membrane reassembly At A Glance
| GO ID | GO:0031468 |
|---|---|
| GO term | nuclear membrane reassembly |
| Ontology | biological_process |
| Synonym | nuclear envelope reassembly |
| Major function | Reformation of nuclear membranes after breakdown during a normal process |
| Related processes | Mitotic nuclear envelope reassembly, nuclear pore complex reassembly, chromatin decondensation |
| Key regulators | Dephosphorylation events, VCP/p97, VCPIP1, emerin |
| Disease relevance | Cancer, laminopathies, replication stress, genome instability |
What Is GO:0031468?
According to the Gene Ontology, nuclear membrane reassembly (GO:0031468) is defined as the reformation of the nuclear membranes following their breakdown in the context of a normal process. This process is also known as nuclear envelope reassembly. It encompasses the re-establishment of the inner and outer nuclear membranes, the reformation of nuclear pore complexes, and the restoration of the nuclear lamina, ensuring the nuclear compartment is functionally restored after events such as mitosis.
Why Is nuclear membrane reassembly Important in Cell Biology?
Nuclear membrane reassembly is fundamental for maintaining genome integrity and cellular function after cell division. Failure of this process can result in persistent DNA damage, replication stress, and aberrant nuclear morphology, which are hallmarks of cancer and premature aging disorders. Understanding the molecular mechanisms of nuclear membrane reassembly provides insights into basic cell biology and offers potential therapeutic targets for diseases characterized by nuclear envelope defects.
• Maintains genome stability by re-establishing the nuclear barrier after mitosis.
• Prevents replication stress and DNA damage by ensuring timely nuclear envelope reformation.
• Regulates nucleocytoplasmic transport through reassembly of nuclear pore complexes.
• Involved in the pathogenesis of laminopathies and other nuclear envelope-related diseases.
• Dysregulation is associated with cancer progression and chemoresistance.
• Provides a model for studying membrane dynamics and organelle biogenesis.
• Key for understanding cell cycle checkpoints and post-mitotic cellular functions.
• Offers targets for CRISPR-based functional genomics and drug discovery.
What Happens During nuclear membrane reassembly?
Initiation and membrane reformation
In simple terms: After the nuclear envelope breaks down during mitosis, it starts to rebuild around the separated chromosomes.
Nuclear membrane reassembly begins in late mitosis, when membrane vesicles and endoplasmic reticulum-derived membranes are recruited to the chromatin surface. This process is triggered by the dephosphorylation of mitotic kinases and the removal of inhibitory phosphorylations on nuclear envelope proteins. The small GTPase Ran and its effectors play a role in directing membrane assembly around chromatin.
Nuclear pore complex reassembly
In simple terms: The tiny channels that control what goes in and out of the nucleus are rebuilt into the new nuclear envelope.
Following membrane reformation, nuclear pore complexes (NPCs) are reassembled and inserted into the newly formed nuclear envelope. This step is essential for restoring nucleocytoplasmic transport and involves the recruitment of nucleoporins in a sequential manner. The process is regulated by phosphorylation and dephosphorylation events that coordinate with the cell cycle.
Chromatin decondensation and nuclear expansion
In simple terms: The tightly packed chromosomes loosen up, and the nucleus grows as it resumes its normal functions.
After the nuclear envelope is sealed, chromatin decondenses, and the nucleus expands. This expansion requires membrane addition and is coupled with the re-establishment of the nuclear lamina. Defects in this step can lead to nuclear blebbing and genome instability.
Quality control and repair
In simple terms: The cell checks for any damage to the new nuclear envelope and fixes it to prevent problems.
Nuclear envelope reassembly is monitored by quality control mechanisms that detect and repair defects such as ruptures or incomplete sealing. Proteins involved in DNA repair, such as those in the TMEJ pathway, contribute to suppressing replication stress-induced nuclear envelope reassembly defects. The crosstalk between mitotic reassembly and repair of the nuclear envelope ensures genomic integrity.
Key Genes Involved in GO:0031468 nuclear membrane reassembly
The following genes and proteins have been implicated in nuclear membrane reassembly based on published literature.
| Gene | Major Role | Research Relevance |
|---|---|---|
| EMD | Emerin, inner nuclear membrane protein | Mutations cause Emery-Dreifuss muscular dystrophy; involved in nuclear envelope stability |
| VCP | AAA-ATPase p97, involved in membrane fusion and protein degradation | Regulates post-mitotic Golgi and nuclear envelope reassembly |
| VCPIP1 | Deubiquitinase that interacts with VCP/p97 | Required for post-mitotic Golgi reassembly; potential role in nuclear envelope reassembly |
| LMNA | Lamin A/C, nuclear lamina proteins | Mutations cause laminopathies; essential for nuclear envelope integrity |
| NUP153 | Nuclear pore complex protein | Involved in NPC reassembly and nucleocytoplasmic transport |
| RAN | Small GTPase | Regulates nuclear envelope and NPC assembly around chromatin |
| TMEJ factors | Polymerase theta-mediated end joining | Suppresses replication stress-induced nuclear envelope reassembly defects |
| CHMP7 | ESCRT-III component | Mediates nuclear envelope repair and reassembly |
| LEM2 | Inner nuclear membrane protein | Interacts with CHMP7 for nuclear envelope sealing |
| BAF | Barrier-to-autointegration factor | Binds DNA and helps recruit nuclear envelope proteins |
| AKAP450 | Centrosomal protein | Involved in nuclear envelope reassembly through membrane trafficking |
| PP1 | Protein phosphatase 1 | Dephosphorylates mitotic substrates to promote reassembly |
| PP2A | Protein phosphatase 2A | Regulates dephosphorylation events in nuclear reassembly |
| Importin beta | Nuclear transport receptor | Regulates membrane fusion and NPC assembly |
| RanGAP1 | Ran GTPase activating protein | Controls Ran gradient for reassembly |
| Nup98 | Nucleoporin | Facilitates NPC reassembly and gene regulation |
| LBR | Lamin B receptor | Anchors lamina to inner nuclear membrane |
How Is nuclear membrane reassembly Regulated?
Nuclear membrane reassembly is regulated by cell cycle-dependent phosphorylation and dephosphorylation. Mitotic kinases such as CDK1 phosphorylate nuclear envelope proteins to trigger disassembly, while phosphatases including PP1 and PP2A reverse these modifications to promote reassembly. The AAA-ATPase VCP/p97 and its adaptor VCPIP1 are required for post-mitotic membrane fusion events. Additionally, the ESCRT-III machinery, including CHMP7, mediates nuclear envelope sealing and repair. DNA repair pathways, such as TMEJ, influence reassembly by resolving replication stress.
nuclear membrane reassembly and Human Disease
| Gene | Disease / Biology | Potential Experimental Model |
|---|---|---|
| EMD | Emery-Dreifuss muscular dystrophy | Knockout or point mutation in human cell lines |
| LMNA | Laminopathies, Hutchinson-Gilford progeria | Knock-in of disease mutations in iPSCs |
| TMEJ factors | Replication stress, cancer | Knockout in cancer cell lines |
| CHMP7 | Nuclear envelope repair defects | Overexpression or knockout in HeLa cells |
| VCP | IBMPFD, neurodegeneration | Point mutation knock-in in neuronal cells |
Cancer and genome instability
Defects in nuclear membrane reassembly can lead to persistent DNA damage and replication stress, contributing to genome instability and cancer progression. TMEJ-mediated DNA repair suppresses replication stress-induced nuclear envelope reassembly defects, and its loss is associated with increased sensitivity to replication stress.
Laminopathies and muscular dystrophy
Mutations in genes encoding nuclear envelope proteins such as EMD (emerin) and LMNA cause Emery-Dreifuss muscular dystrophy and other laminopathies, highlighting the importance of nuclear membrane integrity.
Nuclear envelope repair defects
Impaired crosstalk between mitotic reassembly and repair of the nuclear envelope can result in nuclear rupture and aberrant nuclear morphology, which are linked to premature aging and degenerative diseases.
From nuclear membrane reassembly-Related Genes to Experimental Models
| Research Question | Suitable Model |
|---|---|
| Does gene X regulate nuclear membrane reassembly? | CRISPR knockout in HeLa or U2OS cells followed by imaging |
| What is the role of a specific phosphorylation site? | Point mutation knock-in of phospho-deficient or phospho-mimetic alleles |
| How does a disease mutation affect reassembly? | Knock-in of patient mutations in iPSCs or cell lines |
| Where does a protein localize during reassembly? | Tagged knock-in with fluorescent protein |
| Does overexpression of gene Y accelerate reassembly? | Overexpression via lentiviral transduction |
| Which genes are essential for reassembly? | Genome-wide CRISPR library screening |
How to Study the nuclear membrane reassembly Process
| Method | What It Measures | Typical Application |
|---|---|---|
| Live-cell fluorescence microscopy | Dynamics of nuclear envelope reassembly | Visualizing GFP-tagged nuclear envelope proteins |
| Phosphoproteomics | Changes in phosphorylation during mitosis | Identifying dephosphorylation targets |
| CRISPR knockout screening | Gene essentiality for reassembly | Identifying novel regulators |
| Proximity ligation assay | Protein-protein interactions | Detecting VCPIP1-VCP interaction |
| Electron microscopy | Ultrastructure of nuclear envelope | Observing membrane fusion intermediates |
| RNA-seq | Transcriptional changes | Measuring gene expression during reassembly |
| Western blot | Protein levels and modifications | Validating knockdown or knockout |
| Immunofluorescence | Localization of proteins | Confirming nuclear envelope recruitment |
Live-cell imaging
Fluorescently tagged nuclear envelope and chromatin markers allow real-time visualization of nuclear membrane reassembly dynamics after mitosis.
Proteomics and phosphoproteomics
Mass spectrometry-based approaches identify changes in protein composition and phosphorylation states during reassembly, revealing key regulators.
CRISPR screening
Genome-wide CRISPR knockout or activation screens can identify genes required for efficient nuclear membrane reassembly under stress conditions.
Electron microscopy
Electron microscopy provides ultrastructural details of nuclear envelope reformation and NPC insertion.
How CRISPR Can Be Used to Study GO:0031468 nuclear membrane reassembly
Knockout
CRISPR knockout of candidate genes (e.g., EMD, VCP, CHMP7) in cell lines allows assessment of their requirement for nuclear membrane reassembly. Knockout cells can be synchronized and imaged to quantify reassembly defects.
Point Mutation
Point mutations can be introduced to mimic phosphorylation or dephosphorylation states of key regulators, such as PP1 targets, to dissect their role in reassembly.
Knock-in
Knock-in of disease-associated mutations (e.g., LMNA, EMD) or fluorescent tags enables study of mutant protein behavior during reassembly in a physiological context.
Overexpression
Overexpression of genes such as VCPIP1 or CHMP7 can test whether increased levels enhance or disrupt reassembly, providing gain-of-function insights.
How EDITGENE Supports nuclear membrane reassembly Research
Researchers studying nuclear membrane reassembly-related genes often need to determine whether a candidate gene is causally involved in the process or merely correlated with it. EDITGENE provides custom CRISPR cell models to enable such causal experiments.
Contact EDITGENE today to design your custom CRISPR model for nuclear membrane reassembly research.
Frequently Asked Questions About nuclear membrane reassembly
What is nuclear membrane reassembly?
Nuclear membrane reassembly (GO:0031468) is the process by which the nuclear membranes reform after their breakdown during a normal cellular event, such as mitosis.
What genes are involved in nuclear membrane reassembly?
Key genes include EMD, LMNA, VCP, VCPIP1, CHMP7, LEM2, and TMEJ factors, among others.
What is the GO ID for nuclear membrane reassembly?
The Gene Ontology ID is GO:0031468.
Why is nuclear membrane reassembly important?
It is essential for genome stability, nucleocytoplasmic transport, and preventing diseases such as cancer and laminopathies.
How is nuclear membrane reassembly regulated?
It is regulated by dephosphorylation events, VCP/p97, VCPIP1, and ESCRT-III machinery.
What diseases are associated with defective nuclear membrane reassembly?
Cancer, Emery-Dreifuss muscular dystrophy, laminopathies, and premature aging disorders.
What methods are used to study nuclear membrane reassembly?
Live-cell imaging, proteomics, CRISPR screening, and electron microscopy.
Can CRISPR be used to study nuclear membrane reassembly?
Yes, CRISPR knockout, point mutation, knock-in, and overexpression models are powerful tools for dissecting gene function in this process.
What is the role of VCP/p97 in nuclear membrane reassembly?
VCP/p97, along with its adaptor VCPIP1, is involved in post-mitotic membrane fusion events, including Golgi and likely nuclear envelope reassembly.
How does TMEJ affect nuclear membrane reassembly?
TMEJ-mediated DNA repair suppresses replication stress-induced nuclear envelope reassembly defects, linking DNA repair to nuclear envelope integrity.
Conclusion
Nuclear membrane reassembly (GO:0031468) is a fundamental biological process that ensures genome stability and cellular function after mitosis. Research has identified key molecular players and regulatory mechanisms, and linked defects to human diseases such as cancer and laminopathies. Continued investigation using advanced CRISPR models and imaging techniques will further elucidate this process and its therapeutic potential.
References
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- 2. Gant TM et al.. 1997. Nuclear assembly.. Annu Rev Cell Dev Biol 13:669-95 PMID: 9442884
- 3. Archambault V et al.. 2022. Dephosphorylation in nuclear reassembly after mitosis.. Front Cell Dev Biol 10:1012768 PMID: 36268509
- 5. Kutay U et al.. 2021. Mitotic disassembly and reassembly of nuclear pore complexes.. Trends Cell Biol 31(12):1019-1033 PMID: 34294532
- 6. Ye G et al.. 2025. Mitotic DNA repair by TMEJ suppresses replication stress-induced nuclear envelope reassembly defect.. Nat Commun 16(1):8836 PMID: 41044090
- 7. Liao T et al.. 2024. Molecular Basis of VCPIP1 and P97/VCP Interaction Reveals Its Functions in Post-Mitotic Golgi Reassembly.. Adv Sci (Weinh) 11(41):e2403417 PMID: 39234822
- 8. Kono Y et al.. 2024. Crosstalk between mitotic reassembly and repair of the nuclear envelope.. Nucleus 15(1):2352203 PMID: 38780365
