The largest of the membrane-bound organelles, the nucleus first was described in 1710 by Antoni van Leeuwenhoek using a simple microscope. In 1831 the Scottish botanist Robert Brown characterized the organelle in detail, calling it the "nucleus," from the Latin word for "little nut." The nucleus is the site of gene expression and gene regulation.
A distinguishing characteristic of eukaryotes, the nucleus contains the genetic information (genome ) of the cell in the form of its chromosomes. It is within the nucleus that the DNA in the chromosomes is duplicated prior to cell division and where the RNAs are synthesized. Ribosomes are partially assembled around the newly synthesized ribosomal RNAs (rRNA) while still in the nucleus and then transported into the cytoplasm to continue their final assembly. Similarly, messenger RNAs (mRNA) are synthesized, packaged, and subsequently transported to the cytoplasmic ribosomes, where they are translated into protein.
Typically spherical in shape and taking up 10 percent of the volume of a cell, the nucleus is bounded by a double membrane called the nuclear envelope (Figures 1 and 2). Most material passes in and out of the nuclear envelope through large openings called the nuclear pores. The outside surface of the envelope is directly connected to the endoplasmic reticulum of the cytoplasm and is surrounded by a network of cytoplasmic intermediate filaments. The inside surface of the nuclear envelope is lined with the nuclear lamina. Internally, the nucleus contains several structures: the chromosomes themselves, which together constitute the chromatin; the interchromatin compartment; the large nucleolus; and a variety of different granules collectively called the subnuclear bodies, which include Cajal (coiled) bodies, gems, PML bodies, and speckles. Every time a cell divides, the nuclear envelope must break down to release the recently duplicated chromosomes. After the chromosomes have segregated to the new daughter cells, the nucleus and its components must be rebuilt.
If the DNA of each cell were stretched out linearly, it would be over six feet in length. Although the chromosomes of a nucleus appear as a diffuse network in the electron microscope, they are highly compacted into nucleosomal units. Because of nucleosomal folding, the six feet of DNA yields an organelle tightly packed with chromosomal material. Consequently, it was thought that the nucleus in nondividing cells was a fairly static structure, with its various substructures locked into place. Since the 1980s, however, technological advances have permitted investigators to "paint" chromosomes, parts of chromosomes, genes, proteins, RNAs, or subnuclear bodies with genetically defined fluorescent tags. Combined with new techniques that permit these procedures in living cells, and coupled with time-lapse photography and computer simulation, an entirely different image of the cell nucleus is emerging. The nucleus is now understood to be a dynamic organelle composed of a highly ordered architecture that permits a great deal of structural flexibility and movement of molecules and particles between its various subcompartments.
Each chromosome is specifically anchored through its telomeres to a discrete place on the nuclear envelope by the proteins of the nuclear lamina. Thus each occupies a geographically distinct nuclear space called a chromosomal territory (Figure 2). The homologous chromosomal pairs (matching chromosomes derived from mother and father) do not necessarily lie next to each other.
Chromosomal territories are separated by channels of open nucleoplasm called the interchromatin compartment. Within each territory, DNA can be highly condensed (heterochromatin) or less condensed (euchromatin). Heterochromatin, defined as DNA that is not currently undergoing active transcription, can contain important chromosomal elements such as centromeres . Euchromatin are those chromosomal areas more likely to be active in gene transcription. The heterochromatin of any given chromosome is found within its territory close to the nuclear envelope (Figure 1), but can often project into the interior of the nucleus as patches and/or surround the nucleolus. The euchromatin of each territory extends into the center of the nucleus. In addition, those specific areas of euchromatin undergoing active RNA transcription (gene expression) are typically found on the very periphery of the chromosomal territory, at its juncture with the interchromatin channels.
Chromosomal territories contain at least one other known functional subdomain. Those portions of the DNA that replicate late are found near the nuclear envelope, while earlier-replicating DNA is found in the interior of each territory, projecting into the center of the nucleus. Thus each chromosome not only occupies a discrete place in the nucleus, but each is additionally highly organized into different functional subcompartments. The DNA in each chromosome is highly contorted, looping back and forth within its territory. Chromosomes appear capable of shuffling segments to the correct spot within their territories to carry out gene expression or DNA replication. Indeed, painting of chromosomal segments, including specific genes, with fluorescent tags clearly indicates that chromosomes are constantly shifting around within their territories. Thus the architecture of the chromosomal territories, although highly organized, has a considerable degree of flexibility that is closely tied to both gene expression and DNA replication.
The interchromatin (interchromosomal) compartment is best viewed as a series of channels in and around the individual chromosomal territories that are in direct connection with the nuclear pores of the nuclear envelope. It is filled with nucleoplasm containing subnuclear bodies, nuclear proteins, and RNAs, which move rapidly through its channels. It is thought that as RNA is transcribed from genes along the periphery of the chromosomal territory, it drops into the interchromatin compartment for processing, packaging, and transport out of the nucleus through the nuclear pores.
Hormone receptors, histones , and DNA repair enzymes are all known to move actively through these channels, seeking their nuclear targets. Trafficking of molecules is highly efficient; it takes only seconds for a newly synthesized RNA particle to exit through a nuclear pore. Thus the nucleus is a very busy place, with a rapid and continuous exchange of proteins involved in nuclear function and genomic expression occurring both between nuclear compartments and deep within individual compartments, through which access is guaranteed by transportation through the interchromatin compartment.
The most prominent nuclear feature, the nucleolus is a ribosomal factory. To make the large number of ribosomes needed, eukaryotic genomes carry multiple rRNA gene copies. The human genome contains 180 rRNA genes located on the tips of five different chromosomes (chromosomes 13, 14, 15, 21, and 22). Anchored by the opposite end to the nuclear envelope, each in their own chromosomal territory, the tip of these five chromosomal pairs (ten chromosomes in a diploid cell) extend into the center of the nucleus and come together, and the rRNA genes align to form what is called the nucleolar organizer. Transcription of the rRNA genes 28S, 18S, and 5S occurs rapidly. The transcripts are immediately processed and sequentially packaged through multiple stages into ribosomal subunits. The processing is complicated, requiring many cytoplasmic proteins and enzymes that are transported through the nuclear pores, diffusing through the interchromatin compartment until they reach the nucleolus, where they bind and remain. The nucleolus itself is composed of three subdomains: the nucleolar organizer; rRNA in the process of being transcribed, which is seen as dense fibrils; and granules, which are ribosomes very early in the assembly process.
Proteomic analysis indicates that human nucleoli contain at least 271 different proteins of a diverse array of known functions, with 31 percent encoded by unknown genes. This has raised the distinct possibility that the nucleolus performs other functions besides ribosome synthesis. Corroborating data suggest that the nucleolus entraps specific cell-cycle regulatory proteins (such as CDC14), inhibiting their activity until needed. When released from the nucleolus, they regain activity. Nucleoli may also synthesize and/or transport other ribonucleoprotein particles besides the ribosome, and may play a role in the processing and transport of mRNA or tRNA. Because nucleoli are often seen associating with other subnuclear bodies such as Cajal bodies, additional functions are likely.
Although the function of many of the subnuclear bodies remains elusive, they are indeed true nuclear structures. They are seen both by light and electron microscopy and can be studied in living cells through the use of fluorescent tags. They are known to contain complexes of proteins with or without RNA. Like nucleoli, they are not surrounded by a membrane. They often move through interchromatin channels and are thought to represent dynamic complexes that may form and re-form with each other and other nuclear components to process and transport nuclear components.
Cajal (Coiled) Bodies.
By electron microscopy, Cajal bodies are seen as tangled balls of thread. They number one to ten per nucleus, with more seen in growing cells. They are often found in association with nucleoli or specific chromosomal territories. Although their true function remains unknown, their ability to associate regularly with nucleoli has led to speculation that they are somehow involved in processing either mRNA or rRNA.
More tightly coiled, smaller versions of Cajal bodies, gems are frequently seen interacting with Cajal bodies and are distinct structures. They are known to contain a protein called SMN (which stands for "survival of motor neurons") that, when mutated, is responsible for a severe inherited form of a human muscular wasting disease called spinal muscular atrophy. Based upon the known function of the normal SMN protein, it is speculated that gems are involved in trafficking mRNA spliceosome subunits through the nucleus and may indirectly help remove mRNA introns.
Nuclei typically have ten to twenty PML bodies (also known as PODs, Kremer bodies, or ND10) that take the shape of dense rings. They contain proteins that, when mutated, have been identified with such disease processes as retinoblastoma and Bloom's syndrome. Their normal pattern is altered in the nuclei of human acute promyelocytic leukemia. When cells are infected with herpes simplex virus type 1, adenovirus, or human cytomegalovirus, PML bodies are disrupted. Although their function remains unknown, the fact that they are altered in diseased or malignant cells suggests that they play an important role in the normal cell, including growth control and apoptosis .
Speckles (Interchromatin Granules).
Speckles are clusters of dense structures seen by electron microscopy that, when stained with fluorescent tags specific to small nuclear ribonucleoproteins (snRNP), give rise to a "speckled" nucleus. Small nuclear ribonucleoproteins are RNA-protein complexes that are subunits of the spliceosome involved in mRNA intron removal. The twenty to fifty speckles per nuclei are typically found in the interchromatin compartment, where mRNA undergoes processing prior to transport through the nuclear pore and into the cytoplasm .
Completely surrounding the nucleus, the nuclear envelope sequesters the genomic information of the cell, probably protecting it from the various enzymes and processes that occur within the cytoplasm. It is composed of two concentric membranes, each of which has a distinct protein composition: the outer membrane, which faces the cytoplasm; and the inner membrane, facing the nuclear interior. The inner and outer membranes are separated by the perinuclear space. Both the outer membrane and the perinuclear space are continuous with the endoplasmic reticulum and studded with ribosomes. Any proteins made on the nuclear outer membrane-bound ribosomes drop into the perinuclear space and are transported through the inner membrane into the nucleus. The major transport pathway in and out of the nucleus, however, is thought to be through nuclear pores.
The inner membrane is coated with a mesh-like network of intermediate filaments called the nuclear lamina. Various nuclear structures, including the chromosomes, attach directly to the lamina, which is essential for maintaining the overall architecture and function of the nucleus. Mutations in the lamina proteins, lamin and emerin, can cause the chromosomes to dissociate from the nuclear envelope and disrupt the organization and properties of the nuclear pores, both of which result in embryonic death. In humans, other lamin mutations cause several rare, inherited diseases, including Emery-Dreifuss muscular dystrophy, an inherited form of muscular dystrophy, or Dunnigan-type lipodystrophy, a disease that results in loss of adipose tissue and late-onset, insulin-resistant diabetes beginning at puberty. How lamina protein mutations cause these two diseases is unknown.
Perhaps the most startling feature of the nuclear envelope are the very large, basket-like transport structures called the nuclear pores (figure 4). These structures have a molecular weight of 125 million daltons, making them thirty times larger than a ribosome. Composed of 100 to 200 different proteins collectively called nucleoporins, each nuclear pore pierces through both membranes of the nuclear envelope and probably opens into the interchromatin space of the nucleus. Some nucleoporins are structural components of the nuclear pore; others facilitate transport. Each mammalian cell nucleus contains 3,000 to 5,000 of these pores. The large number is needed to transport the tremendous quantity of proteins, enzymes, RNAs, factors, and complexes in and out of the nucleus to maintain its function and integrity. Small molecules, ions, and proteins up to 45,000 daltons passively diffuse through the pores. However, the vast majority of material transported is through a highly controlled process called "gating," which is responsible for keeping complexes such as the ribosomes in the cytoplasm from entering the nucleus.
Some proteins require multiple crossings through the nuclear pore. Ribosomal proteins are first made in the cytoplasm, transported into the nucleus, assembled into ribosome subunits by the nucleolus, and then transported back out into the cytoplasm. Viruses infect nuclei by taking advantage of the presence of nuclear pores. Some can be transported intact, while others "dock" on the cytoplasmic side of the pore and inject their DNA into the nucleus through the pore's opening. Each nuclear pore can both import and export material in one of two ways.
Any protein transported in or out of the nucleus must contain a nuclear localization signal, which is a specific sequence of four to eight amino acids that triggers either nuclear import or export. Each nuclear pore contains nucleoporins that recognize either the import or export signal, called importins or exportins, respectively. Importins, located on the cytoplasmic side of the nuclear pore, bind their import "cargo" and flip or slide it to the inside of the nucleus. They then move back into their original position, ready to "transport" their next "cargo." The opposite happens on the side of the nuclear pore facing the interior of the nucleus. Here, exportins bind proteins within the nucleus carrying the export signal and flip or slide them through the pore and into the cytoplasm. RNA molecules and complexes can also move through the pores, but only if the importins and or exportins recognize them as cargo.
see also Cell Cycle; Chromosome, Eukaryotic; Muscular Dystrophy; Protein Targeting; Ribosome; Telomere.
Diane C. Rein
Alberts, Bruce, et al. "The Cell Nucleus." In Molecular Biology of the Cell, 3rd ed. NewYork: Garland, 1995.
Dundr, Miroslav, and Tom Misteli. "Functional Architecture in the Cell Nucleus."Biochemical Journal 356 (2001): 297-310.
Lamond, Angus I., and William C. Earnshaw. "Structure and Function in the Nucleus." Science 280 (1998): 547-553.
Lewis, Joe D., and David Tollervey. "Like Attracts Like: Getting RNA ProcessingTogether in the Nucleus." Science 288 (2000): 1385-1389.
Olson, Mark O. J., Miroslav Dundr, and Attila Szebeni. "The Nucleolus: An Old Factory with Unexpected Capabilities." Trends in Cell Biology 10 (2000): 189-196.
Pederson, Thoru. "Protein Mobility within the Nucleus: What Are the Right Moves?"Cell 104 (2001): 635-638.
Wilson, Katherine L. "The Nuclear Envelope, Muscular Dystrophy and GeneExpression." Trends in Cell Biology 10 (2000): 125-129.
Wilson, Katherine, et al. "Lamins and Disease: Insights into Nuclear Infrastructure."Cell 104 (2001): 647-650.
Wolffe, Alan P., and Jeffrey C. Hansen. "Nuclear Visions: Functional Flexibility from Structural Instability." Cell (2001) 104: 631-634.
nucleus (in physics)
nucleus, in physics, the extremely dense central core of an atom.
The Nature of the Nucleus
Atomic nuclei are composed of two types of particles, protons and neutrons, which are collectively known as nucleons. A proton is simply the nucleus of an ordinary hydrogen atom, the lightest atom, and has a unit positive charge. A neutron is an uncharged particle of about the same mass as the proton. The number of protons in a given nucleus is the atomic number of that nucleus and determines which chemical element the nucleus will constitute when surrounded by electrons.
The total number of protons and neutrons together in a nucleus is the atomic mass number of the nucleus. Two nuclei may have the same atomic number but different mass numbers, thus constituting different forms, or isotopes, of the same element. The mass number of a given isotope is the nearest whole number to the atomic weight of that isotope and is approximately equal to the atomic weight (in the case of carbon-12, exactly equal).
Size and Density
The nucleus occupies only a tiny fraction of the volume of an atom (the radius of the nucleus being some 10,000 to 100,000 times smaller than the radius of the atom as a whole), but it contains almost all the mass. An idea of the extreme density of the nucleus is revealed by a simple calculation. The radius of the nucleus of hydrogen is on the order of 10-13 cm so that its volume is on the order of 10-39 cm3 (cubic centimeter); its mass is about 10-24 g (gram). Combining these to estimate the density, we have 10-24 g/10-39 cm3 ≅ 1015 g/cm3, or about a thousand trillion times the density of matter at ordinary scales (the density of water is 1 g/cm3).
Mass Defect, Binding Energy, and Nuclear Reactions
When nuclear masses are measured, the mass is always found to be less than the sum of the masses of the individual nucleons bound in the nucleus. The difference between the nuclear mass and the sum of the individual masses is known as the mass defect and is due to the fact that some of the mass must be converted to energy in order to make the nucleus stable. This nuclear binding energy is related to the mass defect by the famous formula from relativity, E = mc2, where E is energy, m is mass, and c is the speed of light. The binding energy of a nucleus increases with increasing mass number.
A more interesting property of a nucleus is the binding energy per nucleon, found by dividing the binding energy by the mass number. The average binding energy per nucleon is observed to increase rapidly with increasing mass number up to a mass number of about 60, then to decrease rather slowly with higher mass numbers. Thus, nuclei with mass numbers around 60 are the most stable, and those of very small or very large mass numbers are the least stable.
Two important phenomena result from this property of nuclei. Nuclear fission is the spontaneous splitting of a nucleus of large mass number into two nuclei of smaller mass numbers. Nuclear fusion, on the other hand, is the combining of two light nuclei to form a heavier single nucleus, again with an increase in the average binding energy per nucleon. In both cases, the change to a stable final state is accompanied by the release of a large amount of energy per unit mass of the reacting materials as compared to the energy released in chemical reactions (see nuclear energy).
Models of the Nucleus
Several models of the nucleus have evolved that fit certain aspects of nuclear behavior, but no single model has successfully described all aspects. One model is based on the fact that certain properties of a nucleus are similar to those of a drop of incompressible liquid. The liquid-drop model has been particularly successful in explaining details of the fission process and in evolving a formula for the mass of a particular nucleus as a function of its atomic number and mass number, the so-called semiempirical mass formula.
Another model is the Fermi gas model, which treats the nucleons as if they were particles of a gas restricted by the Pauli exclusion principle, which allows only two particles of opposite spin to occupy a particular energy level described by the quantum theory. These particle pairs will fill the lowest energy levels first, then successively higher ones, so that the "gas" is one of minimum energy. There are actually two independent Fermi gases, one of protons and one of neutrons. The tendency of nucleons to occupy the lowest possible energy level explains why there is a tendency for the numbers of protons and neutrons to be nearly equal in lighter nuclei. In heavier nuclei the effect of electrostatic repulsion among the larger number of charges from the protons raises the energy of the protons, with the result that there are more neutrons than protons (for uranium-235, for example, there are 143 neutrons and only 92 protons). The pairing of nucleons in energy levels also helps to explain the tendency of nuclei to have even numbers of both protons and neutrons.
Neither the liquid-drop model nor the Fermi gas model, however, can explain the exceptional stability of nuclei having certain values for either the number of protons or the number of neutrons, or both. These so-called magic numbers are 2, 8, 20, 28, 50, 82, and 126. Because of the similarity between this phenomenon and the stability of the noble gases, which have certain numbers of electrons that are bound in closed "shells," a shell model was suggested for the nucleus. There are major differences, however, between the electrons in an atom and the nucleons in a nucleus. First, the nucleus provides a force center for the electrons of an atom, while the nucleus itself has no single force center. Second, there are two different types of nucleons. Third, the assumption of independent particle motion made in the case of electrons is not as easily made for nucleons. The liquid-drop model is in fact based on the assumption of strong forces between the nucleons that considerably constrain their motion. However, these difficulties were solved and a good explanation of the magic numbers achieved on the basis of the shell model, which included the assumption of strong coupling between the spin angular momentum of a nucleon and its orbital angular momentum. Various attempts have been made, with partial success, to construct a model incorporating the best features of both the liquid-drop model and the shell model.
Scientific Notation for the Nucleus and Nuclear Reactions
A nucleus may be represented conveniently by the chemical symbol for the element together with a subscript and superscript for the atomic number and mass number. (The subscript is often omitted, since the element symbol fixes the atomic number.) The nucleus of ordinary hydrogen, i.e., the proton, is represented by 1H1, an alpha particle (a helium nucleus) is 2He4, the most common isotope of chlorine is 17Cl35, and the uranium isotope used in the atomic bomb is 92U235.
Nuclear reactions involving changes in atomic number or mass number can be expressed easily using this notation. For example, when Ernest Rutherford produced the first artificial nuclear reaction (1919), it involved bombarding a nitrogen nucleus with alpha particles and resulted in an isotope of oxygen with the release of a proton: 2He4+7N14→8O17+1H1. Note that the total of the atomic numbers on the left is equal to the total on the right (i.e., 2+7=8+1), and similarly for the mass numbers (4+14=17+1).
Scientific Investigations of the Nucleus
Following the discovery of radioactivity by A. H. Becquerel in 1896, Ernest Rutherford identified two types of radiation given off by natural radioactive substances and named them alpha and beta; a third, gamma, was later identified. In 1911 he bombarded a thin target of gold foil with alpha rays (subsequently identified as helium nuclei) and found that, although most of the alpha particles passed directly through the foil, a few were deflected by large amounts. By a quantitative analysis of his experimental results, he was able to propose the existence of the nucleus and estimate its size and charge.
After the discovery of the neutron in 1932, physicists turned their attention to the understanding of the strong interactions, or strong nuclear force, that bind protons and neutrons together in nuclei. This force must be great enough to overcome the considerable repulsive force existing between several protons because of their electrical charge. It must exist between nucleons without regard to their charge, since it acts equally on protons and neutrons, and it must not extend very far away from the nucleons (i.e., it must be a short-range force), since it has negligible effect on protons or neutrons outside the nucleus.
In 1935 Hideki Yukawa proposed a theory that this nuclear "glue" was produced by the exchange of a particle between nucleons, just as the electromagnetic force is produced by the exchange of a photon between charged particles. The range of a force is dependent on the mass of the particle carrying the force; the greater the mass of the particle, the shorter the range of the force. The range of the electromagnetic force is infinite because the mass of the photon is zero. From the known range of the nuclear force, Yukawa estimated the mass of the hypothetical carrier of the nuclear force to be about 200 times that of the electron. Given the name meson because its mass is between that of the electron and those of the nucleons, this particle was finally observed in 1947 and is now called the pi meson, or pion, to distinguish it from other mesons that have been discovered (see elementary particles).
Both the proton and the neutron are surrounded by a cloud of pions given off and reabsorbed again within an incredibly short interval of time. Certain other mesons are assumed to be created and destroyed in this way as well, all such particles being termed "virtual" because they exist in violation of the law of conservation of energy (see conservation laws) for a very short span of time allowed by the uncertainty principle. It is now known, however, that at a more fundamental level the actual carrier of the strong force is a particle called the gluon.
See G. Gamow, The Atom and Its Nucleus (1961); R. K. Adair, The Great Design: Particles, Fields, and Creation (1987).
In eukaryotic cells, chromosomes are found in a special compartment called the nucleus. The nucleus is a defining feature of eukaryotic cells, which range from single-celled yeasts to plants and humans. In contrast, bacteria and other prokaryotes are more ancient in evolution and lack a nucleus. The development of the nucleus contributed to the evolution of complex life forms by separating transcription (reading of genes , occurring inside the nucleus) from translation (protein synthesis, occurring in the cytoplasm ) and by providing a structural framework for organizing and regulating larger genomes . In multicellular organisms, individual cells can express different subsets of genes and thereby form specialized tissues such as muscle or skin.
The Nuclear Envelope
The nuclear envelope surrounds the nucleus and creates and maintains a special environment inside it. The envelope consists of two nuclear membranes (inner and outer), nuclear pore complexes, and the lamina, a fibrous network. The nuclear membranes form an impermeable barrier. The outer membrane faces the cytoplasm and is part of the endoplasmic reticulum (ER). The inner membrane faces the chromosomes. Movement into and out of the nucleus occurs through pores (holes) where the inner and outer membranes are fused together. However, the pores are not empty; nuclear transport is controlled by nuclear pore complexes, each consisting of about a thousand proteins ("nucleoporins"). Each pore complex is large enough to accommodate the passage of ribosomal subunits, large protein-RNA (ribonucleic acid) complexes, which exit the nucleus after being assembled in the nucleolus.
The third major component of the envelope, the nuclear lamina, is found in multicellular eukaryotes (including humans), but not in single-celled eukaryotes or plants. (The plant nucleus evolved independently; less is known about its structure.) The lamina is a meshwork of fibers, formed by the head-to-tail polymerization of proteins named lamins. These fibers are concentrated near the inner membrane and also extend throughout the nuclear interior. Lamins are a type of intermediate filament protein and are strong yet flexible. Humans have three lamin genes, which through alternative messenger RNA (mRNA) splicing can produce seven "flavors" of A- and B-type lamin proteins. Different cell types, such as muscles and neurons , express different combinations of lamins.
Lamin filaments are key architectural elements in the nucleus. Beside providing structural stability, lamins also provide attachment sites for other proteins inside the nucleus. Biologists are discovering a growing number of proteins that bind to lamins. Lamin-binding proteins such as LAP2, emerin, and LBR are anchored at the inner nuclear membrane and also bind to chromosomes. This results in two-way and three-way attachments between the inner membrane, lamina, and chromosomes.
Three-Dimensional Organization inside the Nucleus
When purified nuclei are treated with salts and enzymes to remove most proteins and DNA, what remains is a three-dimensional filamentous structure named the nuclear matrix. The composition of the matrix, and whether it includes lamins, has been controversial. However, deoxyribonucleic acid (DNA) replication machinery is stably attached to the matrix. Thus, the matrix may provide a scaffold that allows the orderly replication of chromosomal DNA, and possibly other activities inside the nucleus.
Chromosomes fill much of the nuclear interior, with each chromosome occupying its own neighborhood. In differentiated human cells, sectors of each chromosome are structurally compressed to prevent gene expression . This repressed chromatin , termed heterochromatin, is often located near the nuclear envelope. Other sections of chromosomes are loosely extended ("euchromatin"), making these genes available for transcription and mRNA processing at the surface of compact chromatin. Proteins responsible for transcription and mRNA processing are highly mobile and move rapidly within the aqueous spaces between and surrounding the chromatin fibers. There are also two specialized structures inside the nucleus, which are factories for making multiprotein "machines." The nucleolus is the factory where ribosomes (the translational machines) are assembled. Nucleoli form around the genes that encode ribosomal structural RNAs. Cajal bodies (coiled bodies) are smaller round structures that are proposed to be factories for assembling "transcription machines" responsible for transcribing genes into mRNA.
In Multicellular Eukaryotes, the Nucleus Disassembles During Mitosis
In mammalian cells, the nucleus organizes about 0.7 meters (2.3 feet) of DNA inside a sphere approximately 5 microns in diameter. Remarkably, this structure is completely disassembled when mammalian cells undergo mitosis . Nuclear disassembly is triggered by mitotic phosphorylation of key structural proteins, including lamins, lamin-binding proteins, and nucleoporins. Phosphorylation causes these proteins to change conformation and release each other. Released nuclear membranes merge into the ER network, whereas released lamins and nucleoporins disperse throughout the cytoplasm. These components are then recycled to form two nuclear envelopes, soon after the two sets of daughter chromosomes are segregated.
BOVERI, THEODOR (1862–1915)
German biologist whose experiments with sea urchin eggs and embryos showed that the cell nucleus contains some substance that can, by itself, determine what kind of animal an egg will develop into. Boveri rightly predicted that humans inherit traits on the chromosomes.
During nuclear assembly, membranes reattach to chromosomes and fuse to enclose the chromosomes within one unified envelope. Pore complexes assemble and begin importing nuclear proteins that were released during mitosis, including lamins. The lamins reassemble into filaments, and the condensed chromosomes expand as the envelope expands to its full size. Few of these steps are understood at the molecular level.
Defects in Nuclear Envelope Proteins Cause Human Disease
In the nematode worm, C. elegans, which has only one lamin gene, lamins are essential for life. Lamins are also important, either directly or indirectly, for nuclear shape, nuclear stability, chromatin attachment to the envelope, spacing of nuclear pore complexes, chromosome segregation, completion of mitosis, nuclear assembly, and the elongation phase of DNA replication.
In organisms with multiple lamin genes, the "extra" lamins appear to have specialized functions. For example, the lamin A/C gene is expressed mostly in differentiated cells. People who inherit one mutated copy of the lamin A/C gene develop one of three different diseases: the autosomal dominant form of Emery-Dreifuss muscular dystrophy; dilated cardiomyopathy with conduction system disease; or Dunnigan-type familial partial lipodystrophy (loss of fat tissue). Cardiomyopathy and lipodystrophy are correlated with missense mutations that change one amino acid in different regions of lamin A. Missense mutations might prevent lamin A/C from assembling properly, or might prevent its recognition by one or more binding partners. The loss of emerin, a membrane protein that binds lamins A/C, causes the X-linked recessive form of Emery-Dreifuss muscular dystrophy.
These diseases are not yet well understood. However, lamins and laminbinding proteins may provide attachment sites needed by other nuclear proteins. For example, retinoblastoma, a transcriptional repressor critical for cell growth control, associates with the nuclear lamina. Insight into the functions of the nucleus may help to alleviate some diseases.
see also Chromosome, Eukaryotic; DNA; Nuclear Transport; Nucleolus; Replication
Katherine L. Wilson
Cohen, Merav, Kenneth K. Lee, Katherine L. Wilson, and Yosef Gruenbaum. "Transcriptional Repression, Apoptosis, Human Disease and the Functional Evolution of the Nuclear Lamina." Trends In Biochemical Sciences 26 (2001): 41–47.
Gerace, Larry, and Roland Foisner. "Integral Membrane Proteins and Dynamic Organization of the Nuclear Envelope." Trends in Cell Biology 4 (1994): 127–131.
Lamond, Angus I., and William C. Earnshaw. "Structure and Function in the Nucleus." Science 280 (1998): 547–553.
Wilson, Katherine L. "The Nuclear Envelope, Muscular Dystrophy, and Gene Expression." Trends in Cell Biology 10 (2000): 125–129.
The nucleus is the control center that directs the activities of the cell. Most important is its control of cell reproduction and the construction of materials like proteins. The nucleus also functions as the cell's main repository of genetic information in the form of deoxyribonucleic acid (DNA).
A eukaryotic cell is a cell that contains a separate nucleus. Plants, animals, fungi, and some forms of single-celled life are eukaryotic or eukaryotes. Those living things, like bacteria, whose cells do not have a distinct nucleus are called prokaryotes. A eukaryotic cell contains many structures called organelles, each of which has a separate function. The most important organelle in a cell is its nucleus (named after a Latin word meaning "kernel" because it looks like a seed in the center of a fruit). If a cell can be described as a miniature factory in which conditions are carefully regulated, then the nucleus in the cell is the factory's main office or control center. The nucleus is a very busy place as it simultaneously controls many cellular activities, responds to changes in its environment, and helps make ribonucleic acid (RNA). As the heart of every cell, the nucleus is easily seen when a cell is observed with a microscope. Because of its large size, the nucleus is by far the outstanding feature of every cell. It usually appears as a rounded structure near the center of the cell. Besides its size, what makes the nucleus so distinct is that it is surrounded by a double membrane called the nuclear envelope. This keeps the nucleus separate from the rest of the cell's living material called the cytoplasm. This envelope has many tiny openings known as pores that allow certain substances to pass in and out of the nucleus to the rest of the cell.
Inside the nucleus are two important structures: threadlike structures called chromosomes and small, round structures called nucleoli. The chromosomes contain the cell's genetic material called DNA, which contains all the instructions needed to make a cell work. DNA also contains a cell's genes, which are the basic units of heredity. The number of chromosomes a nucleus contains will change from species to species (humans have forty-six chromosomes). Also found in the nucleus are one or more small, round nucleoli (singular, nucleolus) which help the cell make ribosomes. Ribosomes are organelles that play an important role in the manufacture of proteins. The nucleolus sends RNA to the ribosomes, which use amino acids to make proteins. Ribosomes are outside the nucleus. The nucleus of a cell
is therefore the control center of the cell because it directs the cell's activities by controlling the synthesis of production of proteins. It is with these chemicals called proteins that the nucleus actually runs the cell. Proteins are also a key ingredient in the material out of which cells, are made.
1. The centre of an atom, composed of protons and neutrons and accounting for nearly all of its mass. A proton has a positive electrical charge, equal in magnitude to the negative charge of an electron; a neutron carries no electrical charge. The nucleus of the hydrogen atom contains a single proton; uranium, the heaviest naturally occurring element, has 92 protons and 142, 143, and 146 neutrons in isotopes 234, 235, and 238 respectively.
2. A small, solid particle, e.g. of dust, salt, or smoke on to which water vapour will condense. Such particles are called ‘condensation nuclei’ and some of them have hygroscopic properties that encourage condensation in unsaturated air. Other nuclei of a suitable shape, e.g. some clay particles such as kaolinite, probably act as ‘freezing nuclei’ in the initial stage of ice-crystal formation. See also AITKEN NUCLEUS; BERGERON—FINDEISEN THEORY; CONDENSATION NUCLEUS; and ICE NUCLEUS.
3. The double-membrane-bound organelle containing the chromosomes, that is found in most non-dividing eukaryotic cells; it is essential to their long-term survival. It is variously shaped, although it is normally spherical or ovoid. It disappears temporarily during cell division. It is absent from viruses. The chromosomes, though probably intact, are not visible when the cell is in a resting stage (i.e. not dividing). The nucleus also contains nucleoli, small spherical dense bodies made up of ribosomal RNA and protein, which gives it its integrity.
4. See NUCLEATION.
The nucleus is a membrane-bounded organelle found in eukaryotic cells that contains the chromosomes and nucleolus. Intact eukaryotic cells are comprised of a nucleus and cytoplasm . A nuclear envelope encloses chromatin, the nucleolus, and a matrix which fills the nuclear space.
The chromatin consists primarily of the genetic material, DNA , and histone proteins. Chromatin is often arranged in fiber like nucleofilaments.
The nucleolus is a globular cell organelle important to ribosome function and protein synthesis . The nucleolus is a small structure within the nucleus that is rich in ribosomal RNA and proteins. The nucleolus disappears and reorganizes during specific phases of cell division. A nucleus may contain from one to several nucleoli. Nucleoli are associated with protein synthesis and enlarged nucleoli are observed in rapidly growing embryonic tissue (other than cleavage nuclei), cells actively engaged in protein synthesis, and malignant cells. The nuclear matrix itself is also protein rich.
The genetic instructions for an organism are encoded in nuclear DNA that is organized into chromosomes. Eukaryotic chromosomes are composed of proteins and nucleic acids (nucleoprotein). Accordingly, cell division and reproduction require a process by which the DNA (or in some prokaryotes, RNA) can be duplicated and passed to the next generation of cells (daughter cells)
It is possible to obtain genetic replicates through process termed nuclear transplantation. Genetic replicas are cloned by nuclear transplantation. The first cloning program using nuclear transplantation was able, as early a 1952, to produce frogs by nuclear transplantation. Since that time, research programs have produced an number of different species that can be cloned. More recently, sheep (Dolly) and other creatures have been produced by cloning nuclei from adult animal donors.
The cloning procedures for frogs or mammals are similar. Both procedures require the insertion of a nucleus into an egg that has been deprived of its own genetic material. The reconstituted egg, with a new nucleus, develops in accordance with the genetic instructions of the nuclear donor.
There are, of course, cells which do not contain the usual nuclear structures. Embryonic cleavage nuclei (cells forming a blastula) do not have a nucleolus. Because the cells retain the genetic competence to produce nucleoli, gastrula and all later cells contain nucleoli. Another example is found upon examination of mature red blood cells, erythrocytes, that in most mammals are without (devoid) of nuclei. The loss of nuclear material, however, does not preclude the competence to carry oxygen.
See also Cell cycle (eukaryotic), genetic regulation of; DNA (deoxyribonucleic acid)
The term ‘nucleus’ (pl. nuclei) is also used to describe discrete islands of grey matter — clusters of nerve cells — in the brain, for example in the cerebellum, in the hypothalamus, or in the brain stem. These are relay stations for incoming or outgoing nerve fibres or the sites of origin of the cranial nerves.
Alan W. Cuthbert
See cell; DNA; grey matter.
nu·cle·us / ˈn(y)oōklēəs/ • n. (pl. -cle·i / -klēˌī/ ) the central and most important part of an object, movement, or group, forming the basis for its activity and growth: the nucleus of a film-producing industry. ∎ Physics the positively charged central core of an atom, containing most of its mass. ∎ Biol. a dense organelle present in most eukaryotic cells, typically a single rounded structure bounded by a double membrane, containing the genetic material. ∎ Astron. the solid part of the head of a comet. ∎ Anat. a discrete mass of gray matter in the central nervous system.