Cell nucleus

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Cell nucleus_table_infobox_0

Cell biologyCell nucleus_header_cell_0_0_0

In cell biology, the nucleus (pl. nuclei; from Latin nucleus or nuculeus, meaning kernel or seed) is a membrane-bound organelle found in eukaryotic cells. Cell nucleus_sentence_0

Eukaryotes usually have a single nucleus, but a few cell types, such as mammalian red blood cells, have no nuclei, and a few others including osteoclasts have many. Cell nucleus_sentence_1

The main structures making up the nucleus are the nuclear envelope, a double membrane that encloses the entire organelle and isolates its contents from the cellular cytoplasm; and the nuclear matrix (which includes the nuclear lamina), a network within the nucleus that adds mechanical support, much like the cytoskeleton supports the cell as a whole. Cell nucleus_sentence_2

The cell nucleus contains all of the cell's genome, except for the small amount of mitochondrial DNA, organized as multiple long linear DNA molecules in a complex with a large variety of proteins, such as histones, to form chromosomes. Cell nucleus_sentence_3

The genes within these chromosomes are structured in such a way to promote cell function. Cell nucleus_sentence_4

The nucleus maintains the integrity of genes and controls the activities of the cell by regulating gene expression—the nucleus is, therefore, the control center of the cell. Cell nucleus_sentence_5

Because the nuclear envelope is impermeable to large molecules, nuclear pores are required to regulate nuclear transport of molecules across the envelope. Cell nucleus_sentence_6

The pores cross both nuclear membranes, providing a channel through which larger molecules must be actively transported by carrier proteins while allowing free movement of small molecules and ions. Cell nucleus_sentence_7

Movement of large molecules such as proteins and RNA through the pores is required for both gene expression and the maintenance of chromosomes. Cell nucleus_sentence_8

Although the interior of the nucleus does not contain any membrane-bound subcompartments, its contents are not uniform, and a number of nuclear bodies exist, made up of unique proteins, RNA molecules, and particular parts of the chromosomes. Cell nucleus_sentence_9

The best-known of these is the nucleolus, which is mainly involved in the assembly of ribosomes. Cell nucleus_sentence_10

After being produced in the nucleolus, ribosomes are exported to the cytoplasm where they translate messenger RNA. Cell nucleus_sentence_11

Structures Cell nucleus_section_0

The nucleus contains nearly all of the cell's DNA, surrounded by a network of fibrous intermediate filaments and enveloped in a double membrane called the "nuclear envelope". Cell nucleus_sentence_12

The nuclear envelope separates the fluid inside the nucleus, called the nucleoplasm, from the rest of the cell. Cell nucleus_sentence_13

The size of the nucleus depends on the size of the cell it is contained in, with a nucleus typically occupying about 8% of the total cell volume. Cell nucleus_sentence_14

The nucleus is the largest organelle in animal cells. Cell nucleus_sentence_15

In mammalian cells, the average diameter of the nucleus is approximately 6 micrometres (µm). Cell nucleus_sentence_16

Nuclear envelope and pores Cell nucleus_section_1

Main articles: Nuclear envelope and Nuclear pores Cell nucleus_sentence_17

The nuclear envelope consists of two cellular membranes, called the inner and outer nuclear membranes. Cell nucleus_sentence_18

Together, these membranes serve to separate the cells' genetic material from the rest of the cell contents, and allow the nucleus to maintain an environment distinct from the rest of the cell. Cell nucleus_sentence_19

Despite their close apposition around much of the nucleus, the two membranes differ substantially in shape and contents. Cell nucleus_sentence_20

The inner membrane surrounds the nuclear content, providing its defining edge. Cell nucleus_sentence_21

Embedded within the inner membrane, various proteins bind the intermediate filaments that give the nucleus its structure. Cell nucleus_sentence_22

The outer membrane both envelopes the inner membrane, and is continuous with the adjacent endoplasmic reticulum membrane. Cell nucleus_sentence_23

As part of the endoplasmic reticulum membrane, the outer nuclear membrane is studded with ribosomes that are actively translating proteins across membrane. Cell nucleus_sentence_24

The space between the two membranes, called the "perinuclear space", is continuous with the endoplasmic reticulum lumen. Cell nucleus_sentence_25

Nuclear pores, which provide aqueous channels through the envelope, are composed of multiple proteins, collectively referred to as nucleoporins. Cell nucleus_sentence_26

The pores are about 60–80 million daltons in molecular weight and consist of around 50 (in yeast) to several hundred proteins (in vertebrates). Cell nucleus_sentence_27

The pores are 100 nm in total diameter; however, the gap through which molecules freely diffuse is only about 9 nm wide, due to the presence of regulatory systems within the center of the pore. Cell nucleus_sentence_28

This size selectively allows the passage of small water-soluble molecules while preventing larger molecules, such as nucleic acids and larger proteins, from inappropriately entering or exiting the nucleus. Cell nucleus_sentence_29

These large molecules must be actively transported into the nucleus instead. Cell nucleus_sentence_30

The nucleus of a typical mammalian cell will have about 3000 to 4000 pores throughout its envelope, each of which contains an eightfold-symmetric ring-shaped structure at a position where the inner and outer membranes fuse. Cell nucleus_sentence_31

Attached to the ring is a structure called the nuclear basket that extends into the nucleoplasm, and a series of filamentous extensions that reach into the cytoplasm. Cell nucleus_sentence_32

Both structures serve to mediate binding to nuclear transport proteins. Cell nucleus_sentence_33

Most proteins, ribosomal subunits, and some DNAs are transported through the pore complexes in a process mediated by a family of transport factors known as karyopherins. Cell nucleus_sentence_34

Those karyopherins that mediate movement into the nucleus are also called importins, whereas those that mediate movement out of the nucleus are called exportins. Cell nucleus_sentence_35

Most karyopherins interact directly with their cargo, although some use adaptor proteins. Cell nucleus_sentence_36

Steroid hormones such as cortisol and aldosterone, as well as other small lipid-soluble molecules involved in intercellular signaling, can diffuse through the cell membrane and into the cytoplasm, where they bind nuclear receptor proteins that are trafficked into the nucleus. Cell nucleus_sentence_37

There they serve as transcription factors when bound to their ligand; in the absence of a ligand, many such receptors function as histone deacetylases that repress gene expression. Cell nucleus_sentence_38

Nuclear lamina Cell nucleus_section_2

Main article: Nuclear lamina Cell nucleus_sentence_39

In animal cells, two networks of intermediate filaments provide the nucleus with mechanical support: The nuclear lamina forms an organized meshwork on the internal face of the envelope, while less organized support is provided on the cytosolic face of the envelope. Cell nucleus_sentence_40

Both systems provide structural support for the nuclear envelope and anchoring sites for chromosomes and nuclear pores. Cell nucleus_sentence_41

The nuclear lamina is composed mostly of lamin proteins. Cell nucleus_sentence_42

Like all proteins, lamins are synthesized in the cytoplasm and later transported to the nucleus interior, where they are assembled before being incorporated into the existing network of nuclear lamina. Cell nucleus_sentence_43

Lamins found on the cytosolic face of the membrane, such as emerin and nesprin, bind to the cytoskeleton to provide structural support. Cell nucleus_sentence_44

Lamins are also found inside the nucleoplasm where they form another regular structure, known as the nucleoplasmic veil, that is visible using fluorescence microscopy. Cell nucleus_sentence_45

The actual function of the veil is not clear, although it is excluded from the nucleolus and is present during interphase. Cell nucleus_sentence_46

Lamin structures that make up the veil, such as LEM3, bind chromatin and disrupting their structure inhibits transcription of protein-coding genes. Cell nucleus_sentence_47

Like the components of other intermediate filaments, the lamin monomer contains an alpha-helical domain used by two monomers to coil around each other, forming a dimer structure called a coiled coil. Cell nucleus_sentence_48

Two of these dimer structures then join side by side, in an antiparallel arrangement, to form a tetramer called a protofilament. Cell nucleus_sentence_49

Eight of these protofilaments form a lateral arrangement that is twisted to form a ropelike filament. Cell nucleus_sentence_50

These filaments can be assembled or disassembled in a dynamic manner, meaning that changes in the length of the filament depend on the competing rates of filament addition and removal. Cell nucleus_sentence_51

Mutations in lamin genes leading to defects in filament assembly cause a group of rare genetic disorders known as laminopathies. Cell nucleus_sentence_52

The most notable laminopathy is the family of diseases known as progeria, which causes the appearance of premature aging in its sufferers. Cell nucleus_sentence_53

The exact mechanism by which the associated biochemical changes give rise to the aged phenotype is not well understood. Cell nucleus_sentence_54

Chromosomes Cell nucleus_section_3

Main article: Chromosome Cell nucleus_sentence_55

Further information: Nuclear organization Cell nucleus_sentence_56

The cell nucleus contains the majority of the cell's genetic material in the form of multiple linear DNA molecules organized into structures called chromosomes. Cell nucleus_sentence_57

Each human cell contains roughly two meters of DNA. Cell nucleus_sentence_58

During most of the cell cycle these are organized in a DNA-protein complex known as chromatin, and during cell division the chromatin can be seen to form the well-defined chromosomes familiar from a karyotype. Cell nucleus_sentence_59

A small fraction of the cell's genes are located instead in the mitochondria. Cell nucleus_sentence_60

There are two types of chromatin. Cell nucleus_sentence_61

Euchromatin is the less compact DNA form, and contains genes that are frequently expressed by the cell. Cell nucleus_sentence_62

The other type, heterochromatin, is the more compact form, and contains DNA that is infrequently transcribed. Cell nucleus_sentence_63

This structure is further categorized into facultative heterochromatin, consisting of genes that are organized as heterochromatin only in certain cell types or at certain stages of development, and constitutive heterochromatin that consists of chromosome structural components such as telomeres and centromeres. Cell nucleus_sentence_64

During interphase the chromatin organizes itself into discrete individual patches, called chromosome territories. Cell nucleus_sentence_65

Active genes, which are generally found in the euchromatic region of the chromosome, tend to be located towards the chromosome's territory boundary. Cell nucleus_sentence_66

Antibodies to certain types of chromatin organization, in particular, nucleosomes, have been associated with a number of autoimmune diseases, such as systemic lupus erythematosus. Cell nucleus_sentence_67

These are known as anti-nuclear antibodies (ANA) and have also been observed in concert with multiple sclerosis as part of general immune system dysfunction. Cell nucleus_sentence_68

Nucleolus Cell nucleus_section_4

Main article: Nucleolus Cell nucleus_sentence_69

Further information: Nuclear bodies Cell nucleus_sentence_70

The nucleolus is the largest of the discrete densely stained, membraneless structures known as nuclear bodies found in the nucleus. Cell nucleus_sentence_71

It forms around tandem repeats of rDNA, DNA coding for ribosomal RNA (rRNA). Cell nucleus_sentence_72

These regions are called nucleolar organizer regions (NOR). Cell nucleus_sentence_73

The main roles of the nucleolus are to synthesize rRNA and assemble ribosomes. Cell nucleus_sentence_74

The structural cohesion of the nucleolus depends on its activity, as ribosomal assembly in the nucleolus results in the transient association of nucleolar components, facilitating further ribosomal assembly, and hence further association. Cell nucleus_sentence_75

This model is supported by observations that inactivation of rDNA results in intermingling of nucleolar structures. Cell nucleus_sentence_76

In the first step of ribosome assembly, a protein called RNA polymerase I transcribes rDNA, which forms a large pre-rRNA precursor. Cell nucleus_sentence_77

This is cleaved into the subunits 5.8S, 18S, and 28S rRNA. Cell nucleus_sentence_78

The transcription, post-transcriptional processing, and assembly of rRNA occurs in the nucleolus, aided by small nucleolar RNA (snoRNA) molecules, some of which are derived from spliced introns from messenger RNAs encoding genes related to ribosomal function. Cell nucleus_sentence_79

The assembled ribosomal subunits are the largest structures passed through the nuclear pores. Cell nucleus_sentence_80

When observed under the electron microscope, the nucleolus can be seen to consist of three distinguishable regions: the innermost fibrillar centers (FCs), surrounded by the dense fibrillar component (DFC) (that contains fibrillarin and nucleolin), which in turn is bordered by the granular component (GC) (that contains the protein nucleophosmin). Cell nucleus_sentence_81

Transcription of the rDNA occurs either in the FC or at the FC-DFC boundary, and, therefore, when rDNA transcription in the cell is increased, more FCs are detected. Cell nucleus_sentence_82

Most of the cleavage and modification of rRNAs occurs in the DFC, while the latter steps involving protein assembly onto the ribosomal subunits occur in the GC. Cell nucleus_sentence_83

Other nuclear bodies Cell nucleus_section_5

Main article: Nuclear bodies Cell nucleus_sentence_84

Cell nucleus_table_general_1

Subnuclear structure sizesCell nucleus_table_caption_1
Structure nameCell nucleus_header_cell_1_0_0 Structure diameterCell nucleus_header_cell_1_0_1 Ref.Cell nucleus_header_cell_1_0_2
Cajal bodiesCell nucleus_cell_1_1_0 0.2–2.0 µmCell nucleus_cell_1_1_1 Cell nucleus_cell_1_1_2
ClastosomesCell nucleus_cell_1_2_0 0.2-0.5 µmCell nucleus_cell_1_2_1 Cell nucleus_cell_1_2_2
PIKACell nucleus_cell_1_3_0 5 µmCell nucleus_cell_1_3_1 Cell nucleus_cell_1_3_2
PML bodiesCell nucleus_cell_1_4_0 0.2–1.0 µmCell nucleus_cell_1_4_1 Cell nucleus_cell_1_4_2
ParaspecklesCell nucleus_cell_1_5_0 0.5–1.0 µmCell nucleus_cell_1_5_1 Cell nucleus_cell_1_5_2
SpecklesCell nucleus_cell_1_6_0 20–25 nmCell nucleus_cell_1_6_1 Cell nucleus_cell_1_6_2

Besides the nucleolus, the nucleus contains a number of other nuclear bodies. Cell nucleus_sentence_85

These include Cajal bodies, gemini of Cajal bodies, polymorphic interphase karyosomal association (PIKA), promyelocytic leukaemia (PML) bodies, paraspeckles, and splicing speckles. Cell nucleus_sentence_86

Although little is known about a number of these domains, they are significant in that they show that the nucleoplasm is not a uniform mixture, but rather contains organized functional subdomains. Cell nucleus_sentence_87

Other subnuclear structures appear as part of abnormal disease processes. Cell nucleus_sentence_88

For example, the presence of small intranuclear rods has been reported in some cases of nemaline myopathy. Cell nucleus_sentence_89

This condition typically results from mutations in actin, and the rods themselves consist of mutant actin as well as other cytoskeletal proteins. Cell nucleus_sentence_90

Cajal bodies and gems Cell nucleus_section_6

A nucleus typically contains between one and ten compact structures called Cajal bodies or coiled bodies (CB), whose diameter measures between 0.2 µm and 2.0 µm depending on the cell type and species. Cell nucleus_sentence_91

When seen under an electron microscope, they resemble balls of tangled thread and are dense foci of distribution for the protein coilin. Cell nucleus_sentence_92

CBs are involved in a number of different roles relating to RNA processing, specifically small nucleolar RNA (snoRNA) and small nuclear RNA (snRNA) maturation, and histone mRNA modification. Cell nucleus_sentence_93

Similar to Cajal bodies are Gemini of Cajal bodies, or gems, whose name is derived from the Gemini constellation in reference to their close "twin" relationship with CBs. Cell nucleus_sentence_94

Gems are similar in size and shape to CBs, and in fact are virtually indistinguishable under the microscope. Cell nucleus_sentence_95

Unlike CBs, gems do not contain small nuclear ribonucleoproteins (snRNPs), but do contain a protein called survival of motor neuron (SMN) whose function relates to snRNP biogenesis. Cell nucleus_sentence_96

Gems are believed to assist CBs in snRNP biogenesis, though it has also been suggested from microscopy evidence that CBs and gems are different manifestations of the same structure. Cell nucleus_sentence_97

Later ultrastructural studies have shown gems to be twins of Cajal bodies with the difference being in the coilin component; Cajal bodies are SMN positive and coilin positive, and gems are SMN positive and coilin negative. Cell nucleus_sentence_98

PIKA and PTF domains Cell nucleus_section_7

PIKA domains, or polymorphic interphase karyosomal associations, were first described in microscopy studies in 1991. Cell nucleus_sentence_99

Their function remains unclear, though they were not thought to be associated with active DNA replication, transcription, or RNA processing. Cell nucleus_sentence_100

They have been found to often associate with discrete domains defined by dense localization of the transcription factor PTF, which promotes transcription of small nuclear RNA (snRNA). Cell nucleus_sentence_101

PML bodies Cell nucleus_section_8

Promyelocytic leukemia bodies (PML bodies) are spherical bodies found scattered throughout the nucleoplasm, measuring around 0.1–1.0 µm. Cell nucleus_sentence_102

They are known by a number of other names, including nuclear domain 10 (ND10), Kremer bodies, and PML oncogenic domains. Cell nucleus_sentence_103

PML bodies are named after one of their major components, the promyelocytic leukemia protein (PML). Cell nucleus_sentence_104

They are often seen in the nucleus in association with Cajal bodies and cleavage bodies. Cell nucleus_sentence_105

Pml-/- mice, which are unable to create PML bodies, develop normally without obvious ill effects, showing that PML bodies are not required for most essential biological processes. Cell nucleus_sentence_106

Splicing speckles Cell nucleus_section_9

Speckles are subnuclear structures that are enriched in pre-messenger RNA splicing factors and are located in the interchromatin regions of the nucleoplasm of mammalian cells. Cell nucleus_sentence_107

At the fluorescence-microscope level they appear as irregular, punctate structures, which vary in size and shape, and when examined by electron microscopy they are seen as clusters of interchromatin granules. Cell nucleus_sentence_108

Speckles are dynamic structures, and both their protein and RNA-protein components can cycle continuously between speckles and other nuclear locations, including active transcription sites. Cell nucleus_sentence_109

Studies on the composition, structure and behaviour of speckles have provided a model for understanding the functional compartmentalization of the nucleus and the organization of the gene-expression machinery splicing snRNPs and other splicing proteins necessary for pre-mRNA processing. Cell nucleus_sentence_110

Because of a cell's changing requirements, the composition and location of these bodies changes according to mRNA transcription and regulation via phosphorylation of specific proteins. Cell nucleus_sentence_111

The splicing speckles are also known as nuclear speckles (nuclear specks), splicing factor compartments (SF compartments), interchromatin granule clusters (IGCs), and B snurposomes. Cell nucleus_sentence_112

B snurposomes are found in the amphibian oocyte nuclei and in Drosophila melanogaster embryos. Cell nucleus_sentence_113

B snurposomes appear alone or attached to the Cajal bodies in the electron micrographs of the amphibian nuclei. Cell nucleus_sentence_114

IGCs function as storage sites for the splicing factors. Cell nucleus_sentence_115

Paraspeckles Cell nucleus_section_10

Main article: Paraspeckle Cell nucleus_sentence_116

Discovered by Fox et al. Cell nucleus_sentence_117

in 2002, paraspeckles are irregularly shaped compartments in the interchromatin space of the nucleus. Cell nucleus_sentence_118

First documented in HeLa cells, where there are generally 10–30 per nucleus, paraspeckles are now known to also exist in all human primary cells, transformed cell lines, and tissue sections. Cell nucleus_sentence_119

Their name is derived from their distribution in the nucleus; the "para" is short for parallel and the "speckles" refers to the splicing speckles to which they are always in close proximity. Cell nucleus_sentence_120

Paraspeckles sequester nuclear proteins and RNA and thus appear to function as a molecular sponge that is involved in the regulation of gene expression. Cell nucleus_sentence_121

Furthermore, paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. Cell nucleus_sentence_122

They are transcription dependent and in the absence of RNA Pol II transcription, the paraspeckle disappears and all of its associated protein components (PSP1, p54nrb, PSP2, CFI(m)68, and PSF) form a crescent shaped perinucleolar cap in the nucleolus. Cell nucleus_sentence_123

This phenomenon is demonstrated during the cell cycle. Cell nucleus_sentence_124

In the cell cycle, paraspeckles are present during interphase and during all of mitosis except for telophase. Cell nucleus_sentence_125

During telophase, when the two daughter nuclei are formed, there is no RNA Pol II transcription so the protein components instead form a perinucleolar cap. Cell nucleus_sentence_126

Perichromatin fibrils Cell nucleus_section_11

Perichromatin fibrils are visible only under electron microscope. Cell nucleus_sentence_127

They are located next to the transcriptionally active chromatin and are hypothesized to be the sites of active pre-mRNA processing. Cell nucleus_sentence_128

Clastosomes Cell nucleus_section_12

Clastosomes are small nuclear bodies (0.2–0.5 µm) described as having a thick ring-shape due to the peripheral capsule around these bodies. Cell nucleus_sentence_129

This name is derived from the Greek klastos, broken and soma, body. Cell nucleus_sentence_130

Clastosomes are not typically present in normal cells, making them hard to detect. Cell nucleus_sentence_131

They form under high proteolytic conditions within the nucleus and degrade once there is a decrease in activity or if cells are treated with proteasome inhibitors. Cell nucleus_sentence_132

The scarcity of clastosomes in cells indicates that they are not required for proteasome function. Cell nucleus_sentence_133

Osmotic stress has also been shown to cause the formation of clastosomes. Cell nucleus_sentence_134

These nuclear bodies contain catalytic and regulatory subunits of the proteasome and its substrates, indicating that clastosomes are sites for degrading proteins. Cell nucleus_sentence_135

Function Cell nucleus_section_13

The nucleus provides a site for genetic transcription that is segregated from the location of translation in the cytoplasm, allowing levels of gene regulation that are not available to prokaryotes. Cell nucleus_sentence_136

The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the cell cycle. Cell nucleus_sentence_137

The nucleus is an organelle found in eukaryotic cells. Cell nucleus_sentence_138

Inside its fully enclosed nuclear membrane, it contains the majority of the cell's genetic material. Cell nucleus_sentence_139

This material is organized as DNA molecules, along with a variety of proteins, to form chromosomes. Cell nucleus_sentence_140

Cell compartmentalization Cell nucleus_section_14

The nuclear envelope allows the nucleus to control its contents, and separate them from the rest of the cytoplasm where necessary. Cell nucleus_sentence_141

This is important for controlling processes on either side of the nuclear membrane. Cell nucleus_sentence_142

In most cases where a cytoplasmic process needs to be restricted, a key participant is removed to the nucleus, where it interacts with transcription factors to downregulate the production of certain enzymes in the pathway. Cell nucleus_sentence_143

This regulatory mechanism occurs in the case of glycolysis, a cellular pathway for breaking down glucose to produce energy. Cell nucleus_sentence_144

Hexokinase is an enzyme responsible for the first the step of glycolysis, forming glucose-6-phosphate from glucose. Cell nucleus_sentence_145

At high concentrations of fructose-6-phosphate, a molecule made later from glucose-6-phosphate, a regulator protein removes hexokinase to the nucleus, where it forms a transcriptional repressor complex with nuclear proteins to reduce the expression of genes involved in glycolysis. Cell nucleus_sentence_146

In order to control which genes are being transcribed, the cell separates some transcription factor proteins responsible for regulating gene expression from physical access to the DNA until they are activated by other signaling pathways. Cell nucleus_sentence_147

This prevents even low levels of inappropriate gene expression. Cell nucleus_sentence_148

For example, in the case of NF-κB-controlled genes, which are involved in most inflammatory responses, transcription is induced in response to a signal pathway such as that initiated by the signaling molecule TNF-α, binds to a cell membrane receptor, resulting in the recruitment of signalling proteins, and eventually activating the transcription factor NF-κB. Cell nucleus_sentence_149

A nuclear localisation signal on the NF-κB protein allows it to be transported through the nuclear pore and into the nucleus, where it stimulates the transcription of the target genes. Cell nucleus_sentence_150

The compartmentalization allows the cell to prevent translation of unspliced mRNA. Cell nucleus_sentence_151

Eukaryotic mRNA contains introns that must be removed before being translated to produce functional proteins. Cell nucleus_sentence_152

The splicing is done inside the nucleus before the mRNA can be accessed by ribosomes for translation. Cell nucleus_sentence_153

Without the nucleus, ribosomes would translate newly transcribed (unprocessed) mRNA, resulting in malformed and nonfunctional proteins. Cell nucleus_sentence_154

Replication Cell nucleus_section_15

Main article: Eukaryotic DNA replication Cell nucleus_sentence_155

The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the cell cycle. Cell nucleus_sentence_156

It has been found that replication happens in a localised way in the cell nucleus. Cell nucleus_sentence_157

In the S phase of interphase of the cell cycle; replication takes place. Cell nucleus_sentence_158

Contrary to the traditional view of moving replication forks along stagnant DNA, a concept of replication factories emerged, which means replication forks are concentrated towards some immobilised 'factory' regions through which the template DNA strands pass like conveyor belts. Cell nucleus_sentence_159

Gene expression Cell nucleus_section_16

Main article: Gene expression Cell nucleus_sentence_160

See also: Transcription factories Cell nucleus_sentence_161

Gene expression first involves transcription, in which DNA is used as a template to produce RNA. Cell nucleus_sentence_162

In the case of genes encoding proteins, that RNA produced from this process is messenger RNA (mRNA), which then needs to be translated by ribosomes to form a protein. Cell nucleus_sentence_163

As ribosomes are located outside the nucleus, mRNA produced needs to be exported. Cell nucleus_sentence_164

Since the nucleus is the site of transcription, it also contains a variety of proteins that either directly mediate transcription or are involved in regulating the process. Cell nucleus_sentence_165

These proteins include helicases, which unwind the double-stranded DNA molecule to facilitate access to it, RNA polymerases, which bind to the DNA promoter to synthesize the growing RNA molecule, topoisomerases, which change the amount of supercoiling in DNA, helping it wind and unwind, as well as a large variety of transcription factors that regulate expression. Cell nucleus_sentence_166

Processing of pre-mRNA Cell nucleus_section_17

Main article: Post-transcriptional modification Cell nucleus_sentence_167

Newly synthesized mRNA molecules are known as primary transcripts or pre-mRNA. Cell nucleus_sentence_168

They must undergo post-transcriptional modification in the nucleus before being exported to the cytoplasm; mRNA that appears in the cytoplasm without these modifications is degraded rather than used for protein translation. Cell nucleus_sentence_169

The three main modifications are 5' capping, 3' polyadenylation, and RNA splicing. Cell nucleus_sentence_170

While in the nucleus, pre-mRNA is associated with a variety of proteins in complexes known as heterogeneous ribonucleoprotein particles (hnRNPs). Cell nucleus_sentence_171

Addition of the 5' cap occurs co-transcriptionally and is the first step in post-transcriptional modification. Cell nucleus_sentence_172

The 3' poly-adenine tail is only added after transcription is complete. Cell nucleus_sentence_173

RNA splicing, carried out by a complex called the spliceosome, is the process by which introns, or regions of DNA that do not code for protein, are removed from the pre-mRNA and the remaining exons connected to re-form a single continuous molecule. Cell nucleus_sentence_174

This process normally occurs after 5' capping and 3' polyadenylation but can begin before synthesis is complete in transcripts with many exons. Cell nucleus_sentence_175

Many pre-mRNAs can be spliced in multiple ways to produce different mature mRNAs that encode different protein sequences. Cell nucleus_sentence_176

This process is known as alternative splicing, and allows production of a large variety of proteins from a limited amount of DNA. Cell nucleus_sentence_177

Dynamics and regulation Cell nucleus_section_18

Nuclear transport Cell nucleus_section_19

Main article: Nuclear transport Cell nucleus_sentence_178

The entry and exit of large molecules from the nucleus is tightly controlled by the nuclear pore complexes. Cell nucleus_sentence_179

Although small molecules can enter the nucleus without regulation, macromolecules such as RNA and proteins require association karyopherins called importins to enter the nucleus and exportins to exit. Cell nucleus_sentence_180

"Cargo" proteins that must be translocated from the cytoplasm to the nucleus contain short amino acid sequences known as nuclear localization signals, which are bound by importins, while those transported from the nucleus to the cytoplasm carry nuclear export signals bound by exportins. Cell nucleus_sentence_181

The ability of importins and exportins to transport their cargo is regulated by GTPases, enzymes that hydrolyze the molecule guanosine triphosphate (GTP) to release energy. Cell nucleus_sentence_182

The key GTPase in nuclear transport is Ran, which is bound to either GTP or GDP (guanosine diphosphate), depending on whether it is located in the nucleus or the cytoplasm. Cell nucleus_sentence_183

Whereas importins depend on RanGTP to dissociate from their cargo, exportins require RanGTP in order to bind to their cargo. Cell nucleus_sentence_184

Nuclear import depends on the importin binding its cargo in the cytoplasm and carrying it through the nuclear pore into the nucleus. Cell nucleus_sentence_185

Inside the nucleus, RanGTP acts to separate the cargo from the importin, allowing the importin to exit the nucleus and be reused. Cell nucleus_sentence_186

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. Cell nucleus_sentence_187

Specialized export proteins exist for translocation of mature mRNA and tRNA to the cytoplasm after post-transcriptional modification is complete. Cell nucleus_sentence_188

This quality-control mechanism is important due to these molecules' central role in protein translation. Cell nucleus_sentence_189

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. Cell nucleus_sentence_190

Assembly and disassembly Cell nucleus_section_20

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). Cell nucleus_sentence_191

During these events, the structural components of the nucleus — the envelope and lamina — can be systematically degraded. Cell nucleus_sentence_192

In most cells, the disassembly of the nuclear envelope marks the end of the prophase of mitosis. Cell nucleus_sentence_193

However, this disassembly of the nucleus is not a universal feature of mitosis and does not occur in all cells. Cell nucleus_sentence_194

Some unicellular eukaryotes (e.g., yeasts) undergo so-called closed mitosis, in which the nuclear envelope remains intact. Cell nucleus_sentence_195

In closed mitosis, the daughter chromosomes migrate to opposite poles of the nucleus, which then divides in two. Cell nucleus_sentence_196

The cells of higher eukaryotes, however, usually undergo open mitosis, which is characterized by breakdown of the nuclear envelope. Cell nucleus_sentence_197

The daughter chromosomes then migrate to opposite poles of the mitotic spindle, and new nuclei reassemble around them. Cell nucleus_sentence_198

At a certain point during the cell cycle in open mitosis, the cell divides to form two cells. Cell nucleus_sentence_199

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. Cell nucleus_sentence_200

This occurs by the replicated chromosomes, the sister chromatids, attaching to microtubules, which in turn are attached to different centrosomes. Cell nucleus_sentence_201

The sister chromatids can then be pulled to separate locations in the cell. Cell nucleus_sentence_202

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. Cell nucleus_sentence_203

Therefore, the early stages in the cell cycle, beginning in prophase and until around prometaphase, the nuclear membrane is dismantled. Cell nucleus_sentence_204

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 protein kinase. Cell nucleus_sentence_205

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. Cell nucleus_sentence_206

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). Cell nucleus_sentence_207

In many other protists (e.g., ciliates, sporozoans) and fungi, the centrosomes are intranuclear, and their nuclear envelope also does not disassemble during cell division. Cell nucleus_sentence_208

Apoptosis is a controlled process in which the cell's structural components are destroyed, resulting in death of the cell. Cell nucleus_sentence_209

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. Cell nucleus_sentence_210

The destruction of the lamin networks is controlled by specialized apoptotic proteases called caspases, which cleave the lamin proteins and, thus, degrade the nucleus' structural integrity. Cell nucleus_sentence_211

Lamin cleavage is sometimes used as a laboratory indicator of caspase activity in assays for early apoptotic activity. Cell nucleus_sentence_212

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. Cell nucleus_sentence_213

Inhibition of lamin assembly itself is an inducer of apoptosis. Cell nucleus_sentence_214

The nuclear envelope acts as a barrier that prevents both DNA and RNA viruses from entering the nucleus. Cell nucleus_sentence_215

Some viruses require access to proteins inside the nucleus in order to replicate and/or assemble. Cell nucleus_sentence_216

DNA viruses, such as herpesvirus replicate and assemble in the cell nucleus, and exit by budding through the inner nuclear membrane. Cell nucleus_sentence_217

This process is accompanied by disassembly of the lamina on the nuclear face of the inner membrane. Cell nucleus_sentence_218

Disease-related dynamics Cell nucleus_section_21

Initially, it has been suspected that immunoglobulins in general and autoantibodies in particular do not enter the nucleus. Cell nucleus_sentence_219

Now there is a body of evidence that under pathological conditions (e.g. lupus erythematosus) IgG can enter the nucleus. Cell nucleus_sentence_220

Nuclei per cell Cell nucleus_section_22

Most eukaryotic cell types usually have a single nucleus, but some have no nuclei, while others have several. Cell nucleus_sentence_221

This can result from normal development, as in the maturation of mammalian red blood cells, or from faulty cell division. Cell nucleus_sentence_222

Anucleated cells Cell nucleus_section_23

An anucleated cell contains no nucleus and is, therefore, incapable of dividing to produce daughter cells. Cell nucleus_sentence_223

The best-known anucleated cell is the mammalian red blood cell, or erythrocyte, which also lacks other organelles such as mitochondria, and serves primarily as a transport vessel to ferry oxygen from the lungs to the body's tissues. Cell nucleus_sentence_224

Erythrocytes mature through erythropoiesis in the bone marrow, where they lose their nuclei, organelles, and ribosomes. Cell nucleus_sentence_225

The nucleus is expelled during the process of differentiation from an erythroblast to a reticulocyte, which is the immediate precursor of the mature erythrocyte. Cell nucleus_sentence_226

The presence of mutagens may induce the release of some immature "micronucleated" erythrocytes into the bloodstream. Cell nucleus_sentence_227

Anucleated cells can also arise from flawed cell division in which one daughter lacks a nucleus and the other has two nuclei. Cell nucleus_sentence_228

In flowering plants, this condition occurs in sieve tube elements. Cell nucleus_sentence_229

Multinucleated cells Cell nucleus_section_24

Main article: Multinucleate Cell nucleus_sentence_230

Multinucleated cells contain multiple nuclei. Cell nucleus_sentence_231

Most acantharean species of protozoa and some fungi in mycorrhizae have naturally multinucleated cells. Cell nucleus_sentence_232

Other examples include the intestinal parasites in the genus Giardia, which have two nuclei per cell. Cell nucleus_sentence_233

Ciliates have two kinds of nuclei in a single cell, a somatic macronucleus and a germline micronucleus. Cell nucleus_sentence_234

In humans, skeletal muscle cells, called myocytes and syncytium, become multinucleated during development; the resulting arrangement of nuclei near the periphery of the cells allows maximal intracellular space for myofibrils. Cell nucleus_sentence_235

Other multinucleate cells in the human are osteoclasts a type of bone cell. Cell nucleus_sentence_236

Multinucleated and binucleated cells can also be abnormal in humans; for example, cells arising from the fusion of monocytes and macrophages, known as giant multinucleated cells, sometimes accompany inflammation and are also implicated in tumor formation. Cell nucleus_sentence_237

A number of dinoflagellates are known to have two nuclei. Cell nucleus_sentence_238

Unlike other multinucleated cells these nuclei contain two distinct lineages of DNA: one from the dinoflagellate and the other from a symbiotic diatom. Cell nucleus_sentence_239

Evolution Cell nucleus_section_25

As the major defining characteristic of the eukaryotic cell, the nucleus' evolutionary origin has been the subject of much speculation. Cell nucleus_sentence_240

Four major hypotheses have been proposed to explain the existence of the nucleus, although none have yet earned widespread support. Cell nucleus_sentence_241

The first model known as the "syntrophic model" proposes that a symbiotic relationship between the archaea and bacteria created the nucleus-containing eukaryotic cell. Cell nucleus_sentence_242

(Organisms of the Archaea and Bacteria domain have no cell nucleus.) Cell nucleus_sentence_243

It is hypothesized that the symbiosis originated when ancient archaea, similar to modern methanogenic archaea, invaded and lived within bacteria similar to modern myxobacteria, eventually forming the early nucleus. Cell nucleus_sentence_244

This theory is analogous to the accepted theory for the origin of eukaryotic mitochondria and chloroplasts, which are thought to have developed from a similar endosymbiotic relationship between proto-eukaryotes and aerobic bacteria. Cell nucleus_sentence_245

The archaeal origin of the nucleus is supported by observations that archaea and eukarya have similar genes for certain proteins, including histones. Cell nucleus_sentence_246

Observations that myxobacteria are motile, can form multicellular complexes, and possess kinases and G proteins similar to eukarya, support a bacterial origin for the eukaryotic cell. Cell nucleus_sentence_247

A second model proposes that proto-eukaryotic cells evolved from bacteria without an endosymbiotic stage. Cell nucleus_sentence_248

This model is based on the existence of modern planctomycetes bacteria that possess a nuclear structure with primitive pores and other compartmentalized membrane structures. Cell nucleus_sentence_249

A similar proposal states that a eukaryote-like cell, the chronocyte, evolved first and phagocytosed archaea and bacteria to generate the nucleus and the eukaryotic cell. Cell nucleus_sentence_250

The most controversial model, known as viral eukaryogenesis, posits that the membrane-bound nucleus, along with other eukaryotic features, originated from the infection of a prokaryote by a virus. Cell nucleus_sentence_251

The suggestion is based on similarities between eukaryotes and viruses such as linear DNA strands, mRNA capping, and tight binding to proteins (analogizing histones to viral envelopes). Cell nucleus_sentence_252

One version of the proposal suggests that the nucleus evolved in concert with phagocytosis to form an early cellular "predator". Cell nucleus_sentence_253

Another variant proposes that eukaryotes originated from early archaea infected by poxviruses, on the basis of observed similarity between the DNA polymerases in modern poxviruses and eukaryotes. Cell nucleus_sentence_254

It has been suggested that the unresolved question of the evolution of sex could be related to the viral eukaryogenesis hypothesis. Cell nucleus_sentence_255

A more recent proposal, the exomembrane hypothesis, suggests that the nucleus instead originated from a single ancestral cell that evolved a second exterior cell membrane; the interior membrane enclosing the original cell then became the nuclear membrane and evolved increasingly elaborate pore structures for passage of internally synthesized cellular components such as ribosomal subunits. Cell nucleus_sentence_256

History Cell nucleus_section_26

The nucleus was the first organelle to be discovered. Cell nucleus_sentence_257

What is most likely the oldest preserved drawing dates back to the early microscopist Antonie van Leeuwenhoek (1632–1723). Cell nucleus_sentence_258

He observed a "lumen", the nucleus, in the red blood cells of salmon. Cell nucleus_sentence_259

Unlike mammalian red blood cells, those of other vertebrates still contain nuclei. Cell nucleus_sentence_260

The nucleus was also described by Franz Bauer in 1804 and in more detail in 1831 by Scottish botanist Robert Brown in a talk at the Linnean Society of London. Cell nucleus_sentence_261

Brown was studying orchids under the microscope when he observed an opaque area, which he called the "areola" or "nucleus", in the cells of the flower's outer layer. Cell nucleus_sentence_262

He did not suggest a potential function. Cell nucleus_sentence_263

In 1838, Matthias Schleiden proposed that the nucleus plays a role in generating cells, thus he introduced the name "cytoblast" ("cell builder"). Cell nucleus_sentence_264

He believed that he had observed new cells assembling around "cytoblasts". Cell nucleus_sentence_265

Franz Meyen was a strong opponent of this view, having already described cells multiplying by division and believing that many cells would have no nuclei. Cell nucleus_sentence_266

The idea that cells can be generated de novo, by the "cytoblast" or otherwise, contradicted work by Robert Remak (1852) and Rudolf Virchow (1855) who decisively propagated the new paradigm that cells are generated solely by cells ("Omnis cellula e cellula"). Cell nucleus_sentence_267

The function of the nucleus remained unclear. Cell nucleus_sentence_268

Between 1877 and 1878, Oscar Hertwig published several studies on the fertilization of sea urchin eggs, showing that the nucleus of the sperm enters the oocyte and fuses with its nucleus. Cell nucleus_sentence_269

This was the first time it was suggested that an individual develops from a (single) nucleated cell. Cell nucleus_sentence_270

This was in contradiction to Ernst Haeckel's theory that the complete phylogeny of a species would be repeated during embryonic development, including generation of the first nucleated cell from a "monerula", a structureless mass of primordial protoplasm ("Urschleim"). Cell nucleus_sentence_271

Therefore, the necessity of the sperm nucleus for fertilization was discussed for quite some time. Cell nucleus_sentence_272

However, Hertwig confirmed his observation in other animal groups, including amphibians and molluscs. Cell nucleus_sentence_273

Eduard Strasburger produced the same results for plants in 1884. Cell nucleus_sentence_274

This paved the way to assign the nucleus an important role in heredity. Cell nucleus_sentence_275

In 1873, August Weismann postulated the equivalence of the maternal and paternal germ cells for heredity. Cell nucleus_sentence_276

The function of the nucleus as carrier of genetic information became clear only later, after mitosis was discovered and the Mendelian rules were rediscovered at the beginning of the 20th century; the chromosome theory of heredity was therefore developed. Cell nucleus_sentence_277

See also Cell nucleus_section_27

Cell nucleus_unordered_list_0

Credits to the contents of this page go to the authors of the corresponding Wikipedia page: en.wikipedia.org/wiki/Cell nucleus.