Editing Cell nucleus (section)

==Dynamics and regulation==

===Nuclear transport===
{{Main|Nuclear transport}}

[[Image:RanGTPcycle.png|360px|right|thumb|[[Macromolecule]]s, such as [[RNA]] and [[protein]]s, are [[active transport|actively transported]] across the nuclear membrane in a process called the [[Ran (biology)|Ran]]-[[Guanosine triphosphate|GTP]] nuclear transport cycle.]]

The entry and exit of large molecules from the nucleus is tightly controlled by the nuclear pore complexes. Although small molecules can enter the nucleus without regulation,<ref name="Watson">{{cite book | vauthors = Watson JD, Baker TA, Bell SP, Gann A, Levine M, Losick R | title = Molecular Biology of the Gene | publisher = Peason Benjamin Cummings; CSHL Press. | year = 2004 | edition = 5th | chapter = Ch9–10 | isbn = 978-0-8053-9603-4 }}</ref> macromolecules such as RNA and proteins require association karyopherins called [[importin]]s to enter the nucleus and [[exportin]]s to exit. "Cargo" proteins that must be translocated from the cytoplasm to the nucleus contain short amino acid sequences known as [[nuclear localization signal]]s, which are bound by importins, while those transported from the nucleus to the cytoplasm carry [[nuclear export signal]]s bound by exportins. The ability of importins and exportins to transport their cargo is regulated by [[GTPase]]s, enzymes that [[Hydrolysis|hydrolyze]] the molecule guanosine triphosphate (GTP) to release energy. The key GTPase in nuclear transport is [[Ran (protein)|Ran]], which is bound to either GTP or GDP (guanosine diphosphate), depending on whether it is located in the nucleus or the cytoplasm. Whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo.<ref name="Pemberton" />

Nuclear import depends on the importin binding its cargo in the cytoplasm and carrying it through the nuclear pore into the nucleus. Inside the nucleus, RanGTP acts to separate the cargo from the importin, allowing the importin to exit the nucleus and be reused. Nuclear export is similar, as the exportin binds the cargo inside the nucleus in a process facilitated by RanGTP, exits through the nuclear pore, and separates from its cargo in the cytoplasm.<ref name="Cavazza_2015">{{cite journal | vauthors = Cavazza T, Vernos I | title = The RanGTP Pathway: From Nucleo-Cytoplasmic Transport to Spindle Assembly and Beyond | journal = Frontiers in Cell and Developmental Biology | volume = 3 | pages = 82 | date = 2015 | pmid = 26793706 | pmc = 4707252 | doi = 10.3389/fcell.2015.00082 | department = Review | doi-access = free }}</ref>

Specialized export proteins exist for translocation of mature mRNA and tRNA to the cytoplasm after post-transcriptional modification is complete. This quality-control mechanism is important due to these molecules' central role in protein translation. Mis-expression of a protein due to incomplete excision of exons or mis-incorporation of amino acids could have negative consequences for the cell; thus, incompletely modified RNA that reaches the cytoplasm is degraded rather than used in translation.<ref name="Lodish" />

===Assembly and disassembly===
[[File:Mitosis-fluorescent.jpg|thumb|230px|An image of a [[newt]] [[lung]] cell [[staining (biology)|stained]] with [[fluorescent]] [[dye]]s during [[metaphase]]. The [[mitotic spindle]] can be seen, stained green, attached to the two sets of [[chromosome]]s, stained light blue. All chromosomes but one are already at the metaphase plate. ]]

During its lifetime, a nucleus may be broken down or destroyed, either in the process of [[cell division]] or as a consequence of [[apoptosis]] (the process of [[programmed cell death]]). During these events, the structural components of the nucleus&nbsp;— the envelope and lamina&nbsp;— can be systematically degraded.
In most cells, the disassembly of the nuclear envelope marks the end of the [[prophase]] of mitosis. However, this disassembly of the nucleus is not a universal feature of mitosis and does not occur in all cells. Some unicellular eukaryotes (e.g., yeasts) undergo so-called [[closed mitosis]], in which the nuclear envelope remains intact. In closed mitosis, the daughter chromosomes migrate to opposite poles of the nucleus, which then divides in two. The cells of higher eukaryotes, however, usually undergo [[open mitosis]], which is characterized by breakdown of the nuclear envelope. The daughter chromosomes then migrate to opposite poles of the mitotic spindle, and new nuclei reassemble around them.<ref name = "Lodish" />{{rp|854}}

At a certain point during the cell cycle in open mitosis, the cell divides to form two cells. In order for this process to be possible, each of the new daughter cells must have a full set of genes, a process requiring replication of the chromosomes as well as segregation of the separate sets. This occurs by the replicated chromosomes, the [[sister chromatid]]s, attaching to [[microtubule]]s, which in turn are attached to different [[centrosome]]s. The sister chromatids can then be pulled to separate locations in the cell. In many cells, the centrosome is located in the cytoplasm, outside the nucleus; the microtubules would be unable to attach to the chromatids in the presence of the nuclear envelope.<ref name="Lippincott-Schwartz">{{cite journal | vauthors = Lippincott-Schwartz J | title = Cell biology: ripping up the nuclear envelope | journal = Nature | volume = 416 | issue = 6876 | pages = 31–2 | date = March 2002 | pmid = 11882878 | doi = 10.1038/416031a | url = https://zenodo.org/record/1233215 | s2cid = 4431000 | department = Commentary | bibcode = 2002Natur.416...31L | doi-access = free }}</ref> Therefore, the early stages in the cell cycle, beginning in prophase and until around [[prometaphase]], the nuclear membrane is dismantled.<ref name="RGoldman" /> Likewise, during the same period, the nuclear lamina is also disassembled, a process regulated by phosphorylation of the lamins by protein kinases such as the [[CDC2|CDC2 protein kinase]].<ref name="Boulikas">{{cite journal | vauthors = Boulikas T | title = Phosphorylation of transcription factors and control of the cell cycle | journal = Critical Reviews in Eukaryotic Gene Expression | volume = 5 | issue = 1 | pages = 1–77 | year = 1995 | pmid = 7549180 | department = Review }}</ref> Towards the end of the cell cycle, the nuclear membrane is reformed, and around the same time, the nuclear lamina are reassembled by dephosphorylating the lamins.<ref name="Boulikas" />

However, in [[dinoflagellates]], the nuclear envelope remains intact, the centrosomes are located in the cytoplasm, and the microtubules come in contact with chromosomes, whose centromeric regions are incorporated into the nuclear envelope (the so-called closed mitosis with extranuclear spindle). In many other protists (e.g., [[ciliate]]s, [[Apicomplexa|sporozoans]]) and fungi, the centrosomes are intranuclear, and their nuclear envelope also does not disassemble during cell division.<ref name="Boettcher_2013">{{cite journal | vauthors = Boettcher B, Barral Y | title = The cell biology of open and closed mitosis | journal = Nucleus | location = Austin, Tex. | volume = 4 | issue = 3 | pages = 160–5 | date = 2013 | pmid = 23644379 | pmc = 3720745 | doi = 10.4161/nucl.24676 | department = Review }}</ref>

Apoptosis is a controlled process in which the cell's structural components are destroyed, resulting in death of the cell. Changes associated with apoptosis directly affect the nucleus and its contents, for example, in the condensation of chromatin and the disintegration of the nuclear envelope and lamina. The destruction of the lamin networks is controlled by specialized apoptotic [[protease]]s called [[caspase]]s, which cleave the lamin proteins and, thus, degrade the nucleus' structural integrity. Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in [[assay]]s for early apoptotic activity.<ref name="RGoldman" /> Cells that express mutant caspase-resistant lamins are deficient in nuclear changes related to apoptosis, suggesting that lamins play a role in initiating the events that lead to apoptotic degradation of the nucleus.<ref name="RGoldman" /> Inhibition of lamin assembly itself is an inducer of apoptosis.<ref name="Steen">{{cite journal | vauthors = Steen RL, Collas P | title = Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C expression | journal = The Journal of Cell Biology | volume = 153 | issue = 3 | pages = 621–6 | date = April 2001 | pmid = 11331311 | pmc = 2190567 | doi = 10.1083/jcb.153.3.621 | department = Primary }}</ref>

The nuclear envelope acts as a barrier that prevents both DNA and RNA viruses from entering the nucleus. Some viruses require access to proteins inside the nucleus in order to replicate and/or assemble. DNA viruses, such as [[herpesvirus]] replicate and assemble in the cell nucleus, and exit by budding through the inner nuclear membrane. This process is accompanied by disassembly of the lamina on the nuclear face of the inner membrane.<ref name="RGoldman" />

===Disease-related dynamics===
Initially, it has been suspected that [[immunoglobulins]] in general and [[autoantibodies]] in particular do not enter the nucleus. Now there is a body of evidence that under pathological conditions (e.g. [[lupus erythematosus]]) IgG can enter the nucleus.<ref name="pmid17364135">{{cite journal | vauthors = Böhm I | title = IgG deposits can be detected in cell nuclei of patients with both lupus erythematosus and malignancy | journal = Clinical Rheumatology | volume = 26 | issue = 11 | pages = 1877–82 | date = November 2007 | pmid = 17364135 | doi = 10.1007/s10067-007-0597-y | s2cid = 44879431 | department = Primary }}</ref>