Cell Nucleus
Cell Nucleus
Cell Nucleus
l
Nuc
leus
AnAr
tic
lef
ormWi
kipedi
a,t
heFr
eeEnc
ycl
opedi
a
Cell nucleus 1
Cell nucleus
In cell biology, the nucleus (pl. nuclei;
from Latin nucleus or nuculeus,
meaning kernel), also sometimes
referred to as the "control center", is a
membrane-enclosed organelle found in
eukaryotic cells. It contains most of the
cell's genetic material, organized as
multiple long linear DNA molecules in
complex with a large variety of
proteins, such as histones, to form
chromosomes. The genes within these
chromosomes are the cell's nuclear
genome. The function of the nucleus is
to maintain the integrity of these genes
and to control the activities of the cell
by regulating gene expression — the HeLa cells stained for DNA with the Blue Hoechst dye. The central and rightmost cell are
nucleus is therefore the control center in interphase, thus their entire nuclei are labeled. On the left a cell is going through
of the cell. mitosis and its DNA has condensed ready for division.
Entry of material into the nucleus through phagocytosis. The phagosome travels from the
cell membrane to the nucleus, and then is engulfed by the nucleus, releasing its contents.
History
The nucleus was the first organelle to be
discovered. The probably oldest preserved drawing
dates back to the early microscopist Antonie van
Leeuwenhoek (1632 – 1723). He observed a
"Lumen", the nucleus, in the red blood cells of
salmon[1] . Unlike mammalian red blood cells,
Oldest known depiction of cells and their nuclei by Antonie van those of other vertebrates still possess nuclei. The
Leeuwenhoek, 1719. nucleus was also described by Franz Bauer in
1804[2] and in more detail in 1831 by Scottish
botanist Robert Brown in a talk at the Linnean
Society of London. Brown was studying orchids
microscopically when he observed an opaque area,
which he called the areola or nucleus, in the cells
of the flower's outer layer.[3] He did not suggest a
potential function. In 1838 Matthias Schleiden
proposed that the nucleus plays a role in generating
cells, thus he introduced the name "Cytoblast" (cell
builder). He believed that he had observed new
cells assembling around "cytoblasts". Franz Meyen
was a strong opponent of this view having already
described cells multiplying by division and
Drawing of a Chironomus salivary gland cell believing that many cells would have no nuclei.
published by Walther Flemming in 1882. The
The idea that cells can be generated de novo, by
nucleus contains Polytene chromosomes.
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"). The
function of the nucleus remained unclear.[4]
Cell nucleus 3
Between 1876 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. This was the first time it was suggested that an
individual develops from a (single) nucleated cell. 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 mucus ("Urschleim"). Therefore, the necessity
of the sperm nucleus for fertilization was discussed for quite some time. However, Hertwig confirmed his
observation in other animal groups, e.g. amphibians and molluscs. Eduard Strasburger produced the same results for
plants (1884). This paved the way to assign the nucleus an important role in heredity. In 1873 August Weismann
postulated the equivalence of the maternal and paternal germ cells for heredity. 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 developed.[4]
Structures
The nucleus is the largest cellular organelle in animals.[5] In mammalian cells, the average diameter of the nucleus is
approximately 6 micrometers (μm), which occupies about 10% of the total cell volume.[6] The viscous liquid within
it is called nucleoplasm, and is similar in composition to the cytosol found outside the nucleus.[7] It appears as a
dense, roughly spherical organelle.
The eukaryotic cell nucleus. Visible in this diagram are the A cross section of a nuclear pore on the surface of the nuclear
ribosome-studded double membranes of the nuclear envelope, the envelope (1). Other diagram labels show (2) the outer ring, (3)
DNA (complexed as chromatin), and the nucleolus. Within the cell spokes, (4) basket, and (5) filaments.
nucleus is a viscous liquid called nucleoplasm, similar to the
cytoplasm found outside the nucleus.
The nuclear envelope otherwise known as nuclear membrane consists of two cellular membranes, an inner and an
outer membrane, arranged parallel to one another and separated by 10 to 50 nanometers (nm). The nuclear envelope
completely encloses the nucleus and separates the cell's genetic material from the surrounding cytoplasm, serving as
a barrier to prevent macromolecules from diffusing freely between the nucleoplasm and the cytoplasm.[8] The outer
nuclear membrane is continuous with the membrane of the rough endoplasmic reticulum (RER), and is similarly
studded with ribosomes. The space between the membranes is called the perinuclear space and is continuous with the
RER lumen.
Cell nucleus 4
Nuclear pores, which provide aqueous channels through the envelope, are composed of multiple proteins,
collectively referred to as nucleoporins. The pores are about 125 million daltons in molecular weight and consist of
around 50 (in yeast) to 100 proteins (in vertebrates).[5] 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. This size allows the free passage of small water-soluble molecules while preventing larger
molecules, such as nucleic acids and larger proteins, from inappropriately entering or exiting the nucleus. These
large molecules must be actively transported into the nucleus instead. The nucleus of a typical mammalian cell will
have about 3000 to 4000 pores throughout its envelope,[9] each of which contains a donut-shaped,
eightfold-symmetric ring-shaped structure at a position where the inner and outer membranes fuse.[10] 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. Both structures serve to mediate binding to nuclear transport proteins.[5]
Most proteins, ribosomal subunits, and some RNAs are transported through the pore complexes in a process
mediated by a family of transport factors known as karyopherins. Those karyopherins that mediate movement into
the nucleus are also called importins, while those that mediate movement out of the nucleus are called exportins.
Most karyopherins interact directly with their cargo, although some use adaptor proteins.[11] 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. There they serve as transcription factors when bound to their ligand; in the absence of
ligand many such receptors function as histone deacetylases that repress gene expression.[5]
Nuclear lamina
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. Both systems provide structural support for the nuclear envelope and
anchoring sites for chromosomes and nuclear pores.[6]
The nuclear lamina is mostly composed of lamin proteins. Like all proteins, lamins are synthesized in the cytoplasm
and later transported into the nucleus interior, where they are assembled before being incorporated into the existing
network of nuclear lamina.[12] [13] Lamins are also found inside the nucleoplasm where they form another regular
structure, known as the nucleoplasmic veil,[14] that is visible using fluorescence microscopy. The actual function of
the veil is not clear, although it is excluded from the nucleolus and is present during interphase.[15] The lamin
structures that make up the veil bind chromatin and disrupting their structure inhibits transcription of protein-coding
genes.[16]
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. Two of these dimer
structures then join side by side, in an antiparallel arrangement, to form a tetramer called a protofilament. Eight of
these protofilaments form a lateral arrangement that is twisted to form a ropelike filament. 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.[6]
Mutations in lamin genes leading to defects in filament assembly are known as laminopathies. The most notable
laminopathy is the family of diseases known as progeria, which causes the appearance of premature aging in its
sufferers. The exact mechanism by which the associated biochemical changes give rise to the aged phenotype is not
well understood.[17]
Cell nucleus 5
Chromosomes
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. 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. A
small fraction of the cell's genes are located instead in the
mitochondria.
Antibodies to certain types of chromatin organization, particularly nucleosomes, have been associated with a number
of autoimmune diseases, such as systemic lupus erythematosus.[23] 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.[24] As in the case of progeria, the role played by the antibodies in inducing the symptoms of
autoimmune diseases is not obvious.
Nucleolus
The nucleolus is a discrete densely stained structure found in the
nucleus. It is not surrounded by a membrane, and is sometimes
called a suborganelle. It forms around tandem repeats of rDNA,
DNA coding for ribosomal RNA (rRNA). These regions are called
nucleolar organizer regions (NOR). The main roles of the
nucleolus are to synthesize rRNA and assemble ribosomes. 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. This model is supported
by observations that inactivation of rDNA results in intermingling
of nucleolar structures.[25]
An electron micrograph of a cell nucleus, showing the The first step in ribosomal assembly is transcription of the rDNA,
darkly stained nucleolus. by a protein called RNA polymerase I, forming a large pre-rRNA
precursor. This is cleaved into the subunits 5.8S, 18S, and 28S
Cell nucleus 6
rRNA.[26] 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. The assembled ribosomal subunits are the largest structures
passed through the nuclear pores.[5]
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), which in turn is bordered
by the granular component (GC). 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. Most of the cleavage and
modification of rRNAs occurs in the DFC, while the latter steps involving protein assembly onto the ribosomal
subunits occurs in the GC.[21]
|+ Subnuclear structure sizes Besides the nucleolus, the nucleus contains a number of other non-membrane
delineated bodies. These include Cajal bodies, Gemini of coiled bodies, polymorphic interphase karyosomal
association (PIKA), promyelocytic leukaemia (PML) bodies, paraspeckles and splicing speckles. Although little is
known about a number of these domains, they are significant in that they show that the nucleoplasm is not uniform
mixture, but rather contains organized functional subdomains.[29]
Other subnuclear structures appear as part of abnormal disease processes. For example, the presence of small
intranuclear rods have been reported in some cases of nemaline myopathy. This condition typically results from
mutations in actin, and the rods themselves consist of mutant actin as well as other cytoskeletal proteins.[31]
PML bodies
Promyelocytic leukaemia bodies (PML bodies) are spherical bodies found scattered throughout the nucleoplasm,
measuring around 0.2–1.0 µm. They are known by a number of other names, including nuclear domain 10 (ND10),
Kremer bodies, and PML oncogenic domains. They are often seen in the nucleus in association with Cajal bodies
and cleavage bodies. It has been suggested that they play a role in regulating transcription.[29]
Paraspeckles
Discovered by Fox et al. in 2002, paraspeckles are irregularly shaped compartments in the nucleus' interchromatin
space.[36] First documented in HeLa cells, where there are generally 10–30 per nucleus,[37] paraspeckles are now
known to also exist in all human primary cells, transformed cell lines and tissue sections.[38] 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.[37]
Paraspeckles are dynamic structures that are altered in response to changes in cellular metabolic activity. They are
transcription dependent[36] 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. This phenomenon is demonstrated during the cell cycle. In the cell cycle, paraspeckles are present
during interphase and during all of mitosis except for telophase. 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.[38]
Splicing speckles
Sometimes referred to as interchromatin granule clusters or as splicing-factor compartments, speckles are rich in
splicing snRNPs and other splicing proteins necessary for pre-mRNA processing.[39] 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.[40]
Function
The main function of the cell nucleus is to control gene expression and mediate the replication of DNA during the
cell cycle. 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 compartmentalization
The nuclear envelope allows the nucleus to control its contents, and separate them from the rest of the cytoplasm
where necessary. This is important for controlling processes on either side of the nuclear membrane. In some 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. This regulatory
mechanism occurs in the case of glycolysis, a cellular pathway for breaking down glucose to produce energy.
Hexokinase is an enzyme responsible for the first the step of glycolysis, forming glucose-6-phosphate from glucose.
At high concentrations of fructose-6-phosphate, a molecule made later from glucose-6-phosphate, a regulator protein
removes hexokinase to the nucleus,[41] where it forms a transcriptional repressor complex with nuclear proteins to
reduce the expression of genes involved in glycolysis.[42]
Cell nucleus 8
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. This prevents even low levels of inappropriate gene expression. 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. 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.[6]
The compartmentalization allows the cell to prevent translation of unspliced mRNA.[43] Eukaryotic mRNA contains
introns that must be removed before being translated to produce functional proteins. The splicing is done inside the
nucleus before the mRNA can be accessed by ribosomes for translation. Without the nucleus ribosomes would
translate newly transcribed (unprocessed) mRNA resulting in misformed and nonfunctional proteins.
Gene expression
Gene expression first involves transcription, in which DNA is used
as a template to produce RNA. 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. As ribosomes are located outside the nucleus, mRNA
produced needs to be exported.[44]
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. This process normally occurs after 5' capping and 3' polyadenylation but can begin before
synthesis is complete in transcripts with many exons.[5] Many pre-mRNAs, including those encoding antibodies, can
be spliced in multiple ways to produce different mature mRNAs that encode different protein sequences. This
process is known as alternative splicing, and allows production of a large variety of proteins from a limited amount
Cell nucleus 9
of DNA.
Nuclear transport
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,[46]
macromolecules such as RNA and
proteins require association
karyopherins called importins to enter
the nucleus and exportins to exit.
"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
Macromolecules, such as RNA and proteins, are actively transported across the nuclear
by importins, while those transported
membrane in a process called the Ran-GTP nuclear transport cycle.
from the nucleus to the cytoplasm
carry nuclear export signals bound by
exportins. The ability of importins and exportins to transport their cargo is regulated by GTPases, enzymes that
hydrolyze the molecule guanosine triphosphate to release energy. The key GTPase in nuclear transport is Ran, which
can bind 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.[11]
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.
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 the 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.[5]
Cell nucleus 10
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. ciliates, sporozoans)
and fungi the centrosomes are intranuclear, and their nuclear envelope also does not disassemle during cell division.
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 proteases called caspases, 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 assays
for early apoptotic activity.[14] 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.[14] Inhibition of lamin assembly itself is an inducer of apoptosis.[49]
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.[14]
Cell nucleus 11
erythrocyte.[50] The presence of mutagens may induce the release of some mammals, lack nuclei. This occurs as a
normal part of the cells' development.
immature "micronucleated" erythrocytes into the bloodstream.[51] [52]
Anucleated cells can also arise from flawed cell division in which one
daughter lacks a nucleus and the other has two nuclei.
Polynucleated cells contain multiple nuclei. Most Acantharean species of protozoa[53] and some fungi in
mycorrhizae[54] have naturally polynucleated cells. Other examples include the intestinal parasites in the genus
Giardia, which have two nuclei per cell.[55] In humans, skeletal muscle cells, called myocytes, become
polynucleated during development; the resulting arrangement of nuclei near the periphery of the cells allows
maximal intracellular space for myofibrils.[5] Multinucleated 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[56] and are also implicated in tumor formation.[57]
Evolution
As the major defining characteristic of the eukaryotic cell, the nucleus' evolutionary origin has been the subject of
much speculation. Four major theories have been proposed to explain the existence of the nucleus, although none
have yet earned widespread support.[58]
The theory known as the "syntrophic model" proposes that a symbiotic relationship between the archaea and bacteria
created the nucleus-containing eukaryotic cell. 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. 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.[59] The archaeal origin of the nucleus is supported by observations
that archaea and eukarya have similar genes for certain proteins, including histones. 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.[60]
A second model proposes that proto-eukaryotic cells evolved from bacteria without an endosymbiotic stage. This
model is based on the existence of modern planctomycetes bacteria that possess a nuclear structure with primitive
pores and other compartmentalized membrane structures.[61] 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.[62]
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. The suggestion is based on
similarities between eukaryotes and viruses such as linear DNA strands, mRNA capping, and tight binding to
Cell nucleus 12
proteins (analogizing histones to viral envelopes). One version of the proposal suggests that the nucleus evolved in
concert with phagocytosis to form an early cellular "predator".[63] 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.[64] [65] It has been suggested that the unresolved question of the
evolution of sex could be related to the viral eukaryogenesis hypothesis.[66]
Finally, a very recent proposal suggests that traditional variants of the endosymbiont theory are insufficiently
powerful to explain the origin of the eukaryotic nucleus. This model, termed 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.[67]
Further reading
• Goldman, Robert D.; Gruenbaum, Y; Moir, RD; Shumaker, DK; Spann, TP (2002). "Nuclear lamins: building
blocks of nuclear architecture". Genes & Dev. 16 (16): 533–547. doi:10.1101/gad.960502. PMID 11877373.
A review article about nuclear lamins, explaining their structure and various roles
• Görlich, Dirk; Kutay, U (1999). "Transport between the cell nucleus and the cytoplasm". Ann. Rev. Cell Dev.
Biol. 15 (15): 607–660. doi:10.1146/annurev.cellbio.15.1.607. PMID 10611974.
A review article about nuclear transport, explains the principles of the mechanism, and the various transport
pathways
• Lamond, Angus I.; Earnshaw, WC (1998-04-24). "Structure and Function in the Nucleus". Science 280 (5363):
547–553. doi:10.1126/science.280.5363.547. PMID 9554838.
A review article about the nucleus, explaining the structure of chromosomes within the organelle, and
describing the nucleolus and other subnuclear bodies
• Pennisi E. (2004). "Evolutionary biology. The birth of the nucleus". Science 305 (5685): 766–768.
doi:10.1126/science.305.5685.766. PMID 15297641.
A review article about the evolution of the nucleus, explaining a number of different theories
• Pollard, Thomas D.; William C. Earnshaw (2004). Cell Biology. Philadelphia: Saunders. ISBN 0-7216-3360-9.
A university level textbook focusing on cell biology. Contains information on nucleus structure and function,
including nuclear transport, and subnuclear domains
External links
• cellnucleus.com [68] Website covering structure and function of the nucleus from the Department of Oncology at
the University of Alberta.
• The Nuclear Protein Database [69] Information on nuclear components.
• The Nucleus Collection [70] in the Image & Video Library [71] of The American Society for Cell Biology [72]
contains peer-reviewed still images and video clips that illustrate the nucleus.
• Nuclear Envelope and Nuclear Import Section [73] from Landmark Papers in Cell Biology [74], Joseph G. Gall, J.
Richard McIntosh, eds., contains digitized commentaries and links to seminal research papers on the nucleus.
Published online in the Image & Video Library [71] of The American Society for Cell Biology [72]
• Cytoplasmic patterns generated by human antibodies [75]
Cell nucleus 13
References
[1] Leeuwenhoek, A. van: Opera Omnia, seu Arcana Naturae ope exactissimorum Microscopiorum detecta, experimentis variis comprobata,
Epistolis ad varios illustres viros. J. Arnold et Delphis, A. Beman, Lugdinum Batavorum 1719–1730. Cited after: Dieter Gerlach, Geschichte
der Mikroskopie. Verlag Harry Deutsch, Frankfurt am Main, Germany, 2009. ISBN 978-3-8171-1781-9.
[2] Harris, H (1999). The Birth of the Cell. New Haven: Yale University Press.
[3] Brown, Robert (1866). "On the Organs and Mode of Fecundation of Orchidex and Asclepiadea". Miscellaneous Botanical Works I: 511–514.
[4] Cremer, Thomas (1985). Von der Zellenlehre zur Chromosomentheorie. Berlin, Heidelberg, New York, Tokyo: Springer Verlag.
ISBN 3-540-13987-7. Online Version here (http:/ / www. t-cremer. de/ main_de/ cremer/ personen/ info_T_Cremer. htm#book)
[5] Lodish, H; Berk A, Matsudaira P, Kaiser CA, Krieger M, Scott MP, Zipursky SL, Darnell J. (2004). Molecular Cell Biology (5th ed.). New
York: WH Freeman.
[6] Bruce Alberts, Alexander Johnson, Julian Lewis, Martin Raff, Keith Roberts, Peter Walter, ed (2002). Molecular Biology of the Cell, Chapter
4, pages 191-234 (4th ed.). Garland Science.
[7] Clegg JS (February 1984). "Properties and metabolism of the aqueous cytoplasm and its boundaries" (http:/ / ajpregu. physiology. org/ cgi/
pmidlookup?view=reprint& pmid=6364846). Am. J. Physiol. 246 (2 Pt 2): R133–51. PMID 6364846. .
[8] Paine P, Moore L, Horowitz S (1975). "Nuclear envelope permeability". Nature 254 (5496): 109–114. doi:10.1038/254109a0.
PMID 1117994.
[9] Rodney Rhoades, Richard Pflanzer, ed (1996). "Ch3". Human Physiology (3rd ed.). Saunders College Publishing.
[10] Shulga N, Mosammaparast N, Wozniak R, Goldfarb D (2000). "Yeast nucleoporins involved in passive nuclear envelope permeability". J
Cell Biol 149 (5): 1027–1038. doi:10.1083/jcb.149.5.1027. PMID 10831607.
[11] Pemberton L, Paschal B (2005). "Mechanisms of receptor-mediated nuclear import and nuclear export". Traffic 6 (3): 187–198.
doi:10.1111/j.1600-0854.2005.00270.x. PMID 15702987.
[12] Stuurman N, Heins S, Aebi U (1998). "Nuclear lamins: their structure, assembly, and interactions". J Struct Biol 122 (1–2): 42–66.
doi:10.1006/jsbi.1998.3987. PMID 9724605.
[13] Goldman A, Moir R, Montag-Lowy M, Stewart M, Goldman R (1992). "Pathway of incorporation of microinjected lamin A into the nuclear
envelope". J Cell Biol 119 (4): 725–735. doi:10.1083/jcb.119.4.725. PMID 1429833.
[14] Goldman R, Gruenbaum Y, Moir R, Shumaker D, Spann T (2002). "Nuclear lamins: building blocks of nuclear architecture" (http:/ / www.
genesdev. org/ cgi/ content/ full/ 16/ 5/ 533). Genes Dev 16 (5): 533–547. doi:10.1101/gad.960502. PMID 11877373. .
[15] Moir RD, Yoona M, Khuona S, Goldman RD. (2000). "Nuclear Lamins A and B1: Different Pathways of Assembly during Nuclear
Envelope Formation in Living Cells". Journal of Cell Biology 151 (6): 1155–1168. doi:10.1083/jcb.151.6.1155. PMID 11121432.
[16] Spann TP, Goldman AE, Wang C, Huang S, Goldman RD. (2002). "Alteration of nuclear lamin organization inhibits RNA polymerase
II–dependent transcription". Journal of Cell Biology 156 (4): 603–608. doi:10.1083/jcb.200112047. PMID 11854306.
[17] Mounkes LC, Stewart CL (2004). "Aging and nuclear organization: lamins and progeria". Current Opinion in Cell Biology 16: 322–327.
doi:10.1016/j.ceb.2004.03.009. PMID 15145358.
[18] Ehrenhofer-Murray A (2004). "Chromatin dynamics at DNA replication, transcription and repair". Eur J Biochem 271 (12): 2335–2349.
doi:10.1111/j.1432-1033.2004.04162.x. PMID 15182349.
[19] Grigoryev S, Bulynko Y, Popova E (2006). "The end adjusts the means: heterochromatin remodelling during terminal cell differentiation".
Chromosome Res 14 (1): 53–69. doi:10.1007/s10577-005-1021-6. PMID 16506096.
[20] Schardin, Margit; Cremer, T; Hager, HD; Lang, M (December 1985). "Specific staining of human chromosomes in Chinese hamster x man
hybrid cell lines demonstrates interphase chromosome territories" (http:/ / www. springerlink. com/ content/ lv101t8w17306071/ ). Human
Genetics (Springer Berlin / Heidelberg) 71 (4): 281–287. doi:10.1007/BF00388452. PMID 2416668. .
Cell nucleus 14
[21] Lamond, Angus I.; William C. Earnshaw (1998-04-24). "Structure and Function in the Nucleus". Science 280: 547–553.
doi:10.1126/science.280.5363.547. PMID 9554838.
[22] Kurz, A; Lampel, S; Nickolenko, JE; Bradl, J; Benner, A; Zirbel, RM; Cremer, T; Lichter, P (1996). "Active and inactive genes localize
preferentially in the periphery of chromosome territories" (http:/ / intl. jcb. org/ cgi/ content/ abstract/ 135/ 5/ 1195). The Journal of Cell
Biology (The Rockefeller University Press) 135 (5): 1195–1205. doi:10.1083/jcb.135.5.1195. PMID 8947544. PMC 2121085. .
[23] NF Rothfield, BD Stollar (1967). "The Relation of Immunoglobulin Class, Pattern of Antinuclear Antibody, and Complement-Fixing
Antibodies to DNA in Sera from Patients with Systemic Lupus Erythematosus" (http:/ / www. pubmedcentral. nih. gov/ articlerender.
fcgi?tool=pmcentrez& artid=292929). J Clin Invest 46 (11): 1785–1794. doi:10.1172/JCI105669 (inactive 2009-11-14). PMID 4168731.
PMC 292929.
[24] S Barned, AD Goodman, DH Mattson (1995). "Frequency of anti-nuclear antibodies in multiple sclerosis". Neurology 45 (2): 384–385.
PMID 7854544.
[25] Hernandez-Verdun, Daniele (2006). "Nucleolus: from structure to dynamics". Histochem. Cell. Biol 125 (125): 127–137.
doi:10.1007/s00418-005-0046-4.
[26] Lamond, Angus I.; Judith E. Sleeman. "Nuclear substructure and dynamics". Current Biology 13 (21): R825–828.
doi:10.1016/j.cub.2003.10.012. PMID 14588256.
[27] Cioce M, Lamond A. "Cajal bodies: a long history of discovery". Annu Rev Cell Dev Biol 21: 105–131.
doi:10.1146/annurev.cellbio.20.010403.103738. PMID 16212489.
[28] Pollard, Thomas D.; William C. Earnshaw (2004). Cell Biology. Philadelphia: Saunders. ISBN 0-7216-3360-9.
[29] Dundr, Miroslav; Tom Misteli (2001). "Functional architecture in the cell nucleus". Biochem. J. (356): 297–310.
doi:10.1146/annurev.cellbio.20.010403.103738. PMID 11368755.
[30] Fox, Archa. Interview with R. Sundby. Paraspeckle Size. E-mail Correspondence. 2007-03-07.
[31] Goebel, H.H.; I Warlow (January 1997). "Nemaline myopathy with intranuclear rods—intranuclear rod myopathy". Neuromuscular
Disorders 7 (1): 13–19. doi:10.1016/S0960-8966(96)00404-X. PMID 9132135.
[32] Matera AG, Frey MA. (1998). "Coiled Bodies and Gems: Janus or Gemini?". American Journal of Human Genetics 63 (2): 317–321.
doi:10.1086/301992. PMID 9683623.
[33] Matera, A. Gregory (1998). "Of Coiled Bodies, Gems, and Salmon". Journal of Cellular Biochemistry (70): 181–192. doi:10.1086/301992.
PMID 9671224.
[34] Saunders WS, Cooke CA, Earnshaw WC (1991). "Compartmentalization within the nucleus: discovery of a novel subnuclear region.".
Journal of Cellular Biology 115 (4): 919–931. doi:10.1083/jcb.115.4.919. PMID 1955462
[35] Pombo A, Cuello P, Schul W, Yoon J, Roeder R, Cook P, Murphy S (1998). "Regional and temporal specialization in the nucleus: a
transcriptionally active nuclear domain rich in PTF, Oct1 and PIKA antigens associates with specific chromosomes early in the cell cycle".
EMBO J 17 (6): 1768–1778. doi:10.1093/emboj/17.6.1768. PMID 9501098.
[36] Fox, Archa; Lam, YW; Leung, AK; Lyon, CE; Andersen, J; Mann, M; Lamond, AI (2002). "Paraspeckles:A Novel Nuclear Domain" (http:/
/ www. current-biology. com/ content/ article/ abstract?uid=PIIS0960982201006327). Current Biology 12 (1): 13–25.
doi:10.1016/S0960-9822(01)00632-7. PMID 11790299. .
[37] Fox, Archa; Wendy Bickmore (2004). "Nuclear Compartments: Paraspeckles" (http:/ / npd. hgu. mrc. ac. uk/ compartments/ paraspeckles.
html). Nuclear Protein Database. . Retrieved 2007-03-06.
[38] Fox, A. et al. (2005). "P54nrb Forms a Heterodimer with PSP1 That Localizes to Paraspeckles in an RNA-dependent Manner" (http:/ /
www. molbiolcell. org/ cgi/ reprint/ 16/ 11/ 5304). Molecular Biology of the Cell 16: 5304–5315. doi:10.1091/mbc.E05-06-0587.
PMID 16148043. . PMID 16148043
[39] Lamond AI, Spector DL (August 2003). "Nuclear speckles: a model for nuclear organelles". Nat. Rev. Mol. Cell Biol. 4 (8): 605–12.
doi:10.1038/nrm1172. PMID 12923522.
[40] Handwerger, Korie E.; Joseph G. Gall (January 2006). "Subnuclear organelles: new insights into form and function". TRENDS in Cell
Biology 16 (1): 19–26. doi:10.1016/j.tcb.2005.11.005. PMID 16325406.
[41] Lehninger, Albert L.; David L. Nelson, Michael M. Cox. (2000). Lehninger principles of biochemistry (3rd ed.). New York: Worth
Publishers. ISBN 1-57259-931-6.
[42] Moreno F, Ahuatzi D, Riera A, Palomino CA, Herrero P. (2005). "Glucose sensing through the Hxk2-dependent signalling pathway.".
Biochem Soc Trans 33 (1): 265–268. doi:10.1042/BST0330265. PMID 15667322. PMID 15667322
[43] Görlich, Dirk; Ulrike Kutay (1999). "Transport between the cell nucleus and the cytoplasm". Ann. Rev. Cell Dev. Biol. (15): 607–660.
doi:10.1042/BST0330265. PMID 10611974.
[44] Nierhaus, Knud H.; Daniel N. Wilson (2004). Protein Synthesis and Ribosome Structure: Translating the Genome. Wiley-VCH.
ISBN 3527306382.
[45] Nicolini, Claudio A. (1997). Genome Structure and Function: From Chromosomes Characterization to Genes Technology. Springer.
ISBN 0792345657.
[46] Watson, JD; Baker TA, Bell SP, Gann A, Levine M, Losick R. (2004). "Ch9–10". Molecular Biology of the Gene (5th ed.). Peason
Benjamin Cummings; CSHL Press..
[47] Lippincott-Schwartz, Jennifer (2002-03-07). "Cell biology: Ripping up the nuclear envelope". Nature 416 (6876): 31–32.
doi:10.1038/416031a. PMID 11882878.
Cell nucleus 15
[48] Boulikas T (1995). "Phosphorylation of transcription factors and control of the cell cycle". Crit Rev Eukaryot Gene Expr 5 (1): 1–77.
PMID 7549180.
[49] Steen R, Collas P (2001). "Mistargeting of B-type lamins at the end of mitosis: implications on cell survival and regulation of lamins A/C
expression". J Cell Biol 153 (3): 621–626. doi:10.1083/jcb.153.3.621. PMID 11331311.
[50] Skutelsky, E.; Danon D. (June 1970). "Comparative study of nuclear expulsion from the late erythroblast and cytokinesis". J Cell Biol
(60(3)): 625–635. doi:10.1083/jcb.153.3.621. PMID 5422968.
[51] Torous, DK; Dertinger SD, Hall NE, Tometsko CR. (2000). "Enumeration of micronucleated reticulocytes in rat peripheral blood: a flow
cytometric study". Mutat Res (465(1–2)): 91–99. doi:10.1083/jcb.153.3.621. PMID 10708974.
[52] Hutter, KJ; Stohr M. (1982). "Rapid detection of mutagen induced micronucleated erythrocytes by flow cytometry". Histochemistry (75(3)):
353–362. doi:10.1083/jcb.153.3.621. PMID 7141888.
[53] Zettler, LA; Sogin ML, Caron DA (1997). "Phylogenetic relationships between the Acantharea and the Polycystinea: A molecular
perspective on Haeckel's Radiolaria". Proc Natl Acad Sci USA (94): 11411–11416. doi:10.1083/jcb.153.3.621. PMID 9326623.
[54] Horton, TR (2006). "The number of nuclei in basidiospores of 63 species of ectomycorrhizal Homobasidiomycetes". Mycologia (98(2)):
233–238. doi:10.1083/jcb.153.3.621. PMID 16894968.
[55] Adam RD (December 1991). "The biology of Giardia spp" (http:/ / mmbr. asm. org/ cgi/ pmidlookup?view=long& pmid=1779932).
Microbiol. Rev. 55 (4): 706–32. PMID 1779932. PMC 372844. .
[56] McInnes, A; Rennick DM (1988). "Interleukin 4 induces cultured monocytes/macrophages to form giant multinucleated cells". J Exp Med
(167): 598–611. doi:10.1083/jcb.153.3.621. PMID 3258008.
[57] Goldring, SR; Roelke MS, Petrison KK, Bhan AK (1987). "Human giant cell tumors of bone identification and characterization of cell
types". J Clin Invest (79(2)): 483–491. doi:10.1083/jcb.153.3.621. PMID 3027126.
[58] Pennisi E. (2004). "Evolutionary biology. The birth of the nucleus". Science 305 (5685): 766–768. doi:10.1126/science.305.5685.766.
PMID 15297641.
[59] Margulis, Lynn (1981). Symbiosis in Cell Evolution. San Francisco: W. H. Freeman and Company. pp. 206–227. ISBN 0-7167-1256-3.
[60] Lopez-Garcia P, Moreira D. (2006). "Selective forces for the origin of the eukaryotic nucleus". Bioessays 28 (5): 525–533.
doi:10.1002/bies.20413. PMID 16615090.
[61] Fuerst JA. (2005). "Intracellular compartmentation in planctomycetes". Annu Rev Microbiol. 59: 299–328.
doi:10.1146/annurev.micro.59.030804.121258. PMID 15910279.
[62] Hartman H, Fedorov A. (2002). "The origin of the eukaryotic cell: a genomic investigation" (http:/ / www. pubmedcentral. nih. gov/
articlerender. fcgi?tool=pmcentrez& artid=122206). Proc Natl Acad Sci U S A. 99 (3): 1420–1425. doi:10.1073/pnas.032658599.
PMID 11805300. PMC 122206.
[63] Bell PJ. (2001). "Viral eukaryogenesis: was the ancestor of the nucleus a complex DNA virus?" J Mol Biol Sep;53(3):251–256. PMID
11523012
[64] Takemura M. (2001). Poxviruses and the origin of the eukaryotic nucleus. J Mol Evol 52(5):419–425. PMID 11443345
[65] Villarreal L, DeFilippis V (2000). "A hypothesis for DNA viruses as the origin of eukaryotic replication proteins" (http:/ / www.
pubmedcentral. nih. gov/ articlerender. fcgi?tool=pmcentrez& artid=112226). J Virol 74 (15): 7079–7084.
doi:10.1128/JVI.74.15.7079-7084.2000. PMID 10888648. PMC 112226.
[66] Bell PJ. (2006). "Sex and the eukaryotic cell cycle is consistent with a viral ancestry for the eukaryotic nucleus." J Theor Biol 2006
November 7;243(1):54–63. PMID 16846615
[67] de Roos AD (2006). "The origin of the eukaryotic cell based on conservation of existing interfaces". Artif Life 12 (4): 513–523..
doi:10.1162/artl.2006.12.4.513. PMID 16953783.
[68] http:/ / www. cellnucleus. com/ education_main. htm
[69] http:/ / npd. hgu. mrc. ac. uk/ compartments. html
[70] http:/ / cellimages. ascb. org/ cdm4/ browse. php?CISOROOT=/ p4041coll6
[71] http:/ / cellimages. ascb. org/
[72] http:/ / www. ascb. org/
[73] http:/ / cellimages. ascb. org/ u?/ p4041coll11,62
[74] http:/ / cellimages. ascb. org/ cdm4/ browse. php?CISOROOT=%2Fp4041coll11
[75] http:/ / www. antibodypatterns. com/ cytoplasmic. php
Article Sources and Contributors 16
License
Creative Commons Attribution-Share Alike 3.0 Unported
http:/ / creativecommons. org/ licenses/ by-sa/ 3. 0/