Centrosome
Overview
In cell biology
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...

, the centrosome is an organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....

 that serves as the main microtubule organizing center
Microtubule organizing center
The microtubule-organizing center is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell...

 (MTOC) of the animal cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden
Edouard Van Beneden
Edouard Joseph Marie Van Beneden , son of Pierre-Joseph Van Beneden, was a Belgian embryologist, cytologist and marine biologist. He was professor of zoology at the University of Liège. He contributed to cytogenetics by his works on the roundworm Ascaris...

 in 1883
and was described and named in 1888 by Theodor Boveri
Theodor Boveri
-External links:* Fritz Baltzer. . excerpt from . University of California Press, Berkeley; pp. 85–97....

. In the theory of evolution the centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 and plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s use other MTOC structures to organize their microtubules.
Encyclopedia
In cell biology
Cell biology
Cell biology is a scientific discipline that studies cells – their physiological properties, their structure, the organelles they contain, interactions with their environment, their life cycle, division and death. This is done both on a microscopic and molecular level...

, the centrosome is an organelle
Organelle
In cell biology, an organelle is a specialized subunit within a cell that has a specific function, and is usually separately enclosed within its own lipid bilayer....

 that serves as the main microtubule organizing center
Microtubule organizing center
The microtubule-organizing center is a structure found in eukaryotic cells from which microtubules emerge. MTOCs have two main functions: the organization of eukaryotic flagella and cilia and the organization of the mitotic and meiotic spindle apparatus, which separate the chromosomes during cell...

 (MTOC) of the animal cell
Cell (biology)
The cell is the basic structural and functional unit of all known living organisms. It is the smallest unit of life that is classified as a living thing, and is often called the building block of life. The Alberts text discusses how the "cellular building blocks" move to shape developing embryos....

 as well as a regulator of cell-cycle progression. It was discovered by Edouard Van Beneden
Edouard Van Beneden
Edouard Joseph Marie Van Beneden , son of Pierre-Joseph Van Beneden, was a Belgian embryologist, cytologist and marine biologist. He was professor of zoology at the University of Liège. He contributed to cytogenetics by his works on the roundworm Ascaris...

 in 1883
and was described and named in 1888 by Theodor Boveri
Theodor Boveri
-External links:* Fritz Baltzer. . excerpt from . University of California Press, Berkeley; pp. 85–97....

. In the theory of evolution the centrosome is thought to have evolved only in the metazoan lineage of eukaryotic cells. Fungi
Fungus
A fungus is a member of a large group of eukaryotic organisms that includes microorganisms such as yeasts and molds , as well as the more familiar mushrooms. These organisms are classified as a kingdom, Fungi, which is separate from plants, animals, and bacteria...

 and plant
Plant
Plants are living organisms belonging to the kingdom Plantae. Precise definitions of the kingdom vary, but as the term is used here, plants include familiar organisms such as trees, flowers, herbs, bushes, grasses, vines, ferns, mosses, and green algae. The group is also called green plants or...

s use other MTOC structures to organize their microtubules. Although the centrosome has a key role in efficient mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 in animal cells, it is not essential.

Centrosomes are composed of two orthogonally arranged centriole
Centriole
A Centriole is a barrel-shaped cell structure found in most animal eukaryotic cells, though it is absent in higher plants and most fungi. The walls of each centriole are usually composed of nine triplets of microtubules...

s surrounded by an amorphous mass of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 termed the pericentriolar material
Pericentriolar material
Pericentriolar material is an amorphous mass of protein which makes up the part of the centrosome that surrounds the two centrioles. The PCM contains proteins responsible for microtubule nucleation and anchoring including γ-tubulin, pericentrin and ninein....

 (PCM). The PCM contains proteins responsible for microtubule nucleation
Microtubule nucleation
Microtubules are filaments of the cytoskeleton. They typically form through the polymerization of α- and β-tubulin dimers elongating existing microtubules...

 and anchoring including γ-tubulin
Tubulin
Tubulin is one of several members of a small family of globular proteins. The most common members of the tubulin family are α-tubulin and β-tubulin, the proteins that make up microtubules. Each has a molecular weight of approximately 55 kiloDaltons. Microtubules are assembled from dimers of α- and...

, pericentrin and ninein. In general, each centriole of the centrosome is based on a nine triplet
Triplet
-Science:* A series of three nucleotide bases that form Genetic code* J-coupling as part of NMR spectroscopy* Opal in preparation to be a gemstone* Spin triplet in quantum mechanics — as in triplet oxygen, or simply triplet state in general....

 microtubule assembled in a cartwheel structure, and contains centrin
Centrin
Centrins, also known as caltractins, are a family of calcium-binding phosphoproteins found in the centrosome of eukaryotes. Centrins are present in the centrioles and pericentriolar lattice. Human centrin genes are CETN1, CETN2 and CETN3.-Function:...

, cenexin and tektin
Tektin
Tektins are cytoskeletal proteins found in cilia and flagella as structural components of outer doublet microtubules. They are also present in centrioles and basal bodies. They are polymeric in nature, and form filaments....

.

Roles of the centrosome

Centrosomes are associated with the nuclear membrane during prophase
Prophase
Prophase, from the ancient Greek πρό and φάσις , is a stage of mitosis in which the chromatin condenses into a highly ordered structure called a chromosome in which the chromatin becomes visible. This process, called chromatin condensation, is mediated by the condensin complex...

 of the cell cycle. In mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

 the nuclear membrane breaks down and the centrosome nucleated microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

s can interact with the chromosomes to build the mitotic spindle
Mitotic spindle
In cell biology, the spindle fibers are the structure that separates the chromosomes into the daughter cells during cell division. It is part of the cytoskeleton in eukaryotic cells...

.

The mother centriole, the one that was inherited from the mother cell, also has a central role in making cilia and flagella.

The centrosome is copied only once per cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

 so that each daughter cell inherits one centrosome, containing two centrioles (see also: centrosome cycle
Centrosome cycle
Centrosomes are the major microtubule organizing center in mammalian cells. Failure of centrosome regulation can cause mistakes in chromosome segregation and is associated with aneuploidy. A centrosome is composed of two orthogonal cylindrical proteins, called centrioles, which are surrounded...

). The centrosome replicates during the S phase
S phase
S-phase is the part of the cell cycle in which DNA is replicated, occurring between G1 phase and G2 phase. Precise and accurate DNA replication is necessary to prevent genetic abnormalities which often lead to cell death or disease. Due to the importance, the regulatory pathways that govern this...

 of the cell cycle. During the prophase
Prophase
Prophase, from the ancient Greek πρό and φάσις , is a stage of mitosis in which the chromatin condenses into a highly ordered structure called a chromosome in which the chromatin becomes visible. This process, called chromatin condensation, is mediated by the condensin complex...

 in the process of cell division called mitosis
Mitosis
Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets, in two separate nuclei. It is generally followed immediately by cytokinesis, which divides the nuclei, cytoplasm, organelles and cell membrane into two cells containing roughly...

, the centrosomes migrate to opposite poles of the cell. The mitotic spindle then forms between the two centrosomes. Upon division, each daughter cell receives one centrosome. Aberrant numbers of centrosomes in a cell have been associated with cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

. Doubling of a centrosome is similar to DNA replication
DNA replication
DNA replication is a biological process that occurs in all living organisms and copies their DNA; it is the basis for biological inheritance. The process starts with one double-stranded DNA molecule and produces two identical copies of the molecule...

 in two respects: the semiconservative
Semiconservative replication
Semiconservative replication describes the mechanism by which DNA is replicated in all known cells.This mechanism of replication was one of three models originally proposedfor DNA replication:...

 nature of the process and the action of cdk2 as a regulator of the process. But the processes are essentially different in that centrosome doubling does not occur by template reading and assembly. The mother centriole just aids in the accumulation of materials required for the assembly of the daughter centriole.

In animal cells, centrosomes contain two structures called centrioles. Interestingly, centrioles are not required for the progression of mitosis. When the centrioles are irradiated by a laser, mitosis proceeds normally with a morphologically normal spindle. Moreover, development of the fruit fly Drosophila
Drosophila
Drosophila is a genus of small flies, belonging to the family Drosophilidae, whose members are often called "fruit flies" or more appropriately pomace flies, vinegar flies, or wine flies, a reference to the characteristic of many species to linger around overripe or rotting fruit...

is largely normal when centrioles are absent due to a mutation in a gene required for their duplication. In the absence of the centrioles the microtubules of the spindle are focused by motors allowing the formation of a bipolar spindle. Many cells can completely undergo interphase without centrioles.
Unlike centrioles, centrosomes are required for survival of the organism. Acentrosomal cells lack radial arrays of astral microtubules
Astral microtubules
Astral microtubules are a subpopulation of microtubules, which only exist during and immediately before mitosis. They are defined as any microtubule originating from the centrosome which does not connect to a kinetochore. Astral microtubules develop in the actin skeleton and interact with the cell...

. They are also defective in spindle positioning and in ability to establish a central localization site in cytokinesis. The function of centrosome in this context is hypothesized to ensure the fidelity of cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

 because it greatly increases the efficacy. Some cell types arrest in the following cell cycle when centrosomes are absent. This is not a universal phenomenon.

When the nematode C. elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

egg is fertilized the sperm delivers a pair of centrioles. These centrioles will form the centrosomes which will direct the first cell division of the zygote
Zygote
A zygote , or zygocyte, is the initial cell formed when two gamete cells are joined by means of sexual reproduction. In multicellular organisms, it is the earliest developmental stage of the embryo...

 and this will determine its polarity. It is not yet clear whether the role of the centrosome in polarity determination is microtubule dependent or independent.

Centrosome alterations in cancer cells

It was very early identified (at the end of the 19th century) that centrosomes are frequently altered in cancer
Cancer
Cancer , known medically as a malignant neoplasm, is a large group of different diseases, all involving unregulated cell growth. In cancer, cells divide and grow uncontrollably, forming malignant tumors, and invade nearby parts of the body. The cancer may also spread to more distant parts of the...

 cells, by Theodor Boveri
Theodor Boveri
-External links:* Fritz Baltzer. . excerpt from . University of California Press, Berkeley; pp. 85–97....

, the scientist who named the centrosome itself. This initial observation was subsequently extended to many types of human tumors. Centrosome alterations in cancer can be divided in two subgroups, structural or numeric aberrations, yet both can be simultaneously found in a tumor.

Structural aberrations

Usually they appear due to uncontrolled expression of centrosome components, or due to post-translational modifications (such as phosphorylations) which are not adequate for those components. These modifications may produce variations in centrosome size (usually too big, due to an excess of pericentriolar material). On top of this, due to the fact that centrosomal proteins have the tendency to form aggregates, often centrosome-related bodies (CRBs) are observed in ectopic places. Both enlarged centrosomes and CRBs are similar to the centrosomal structures observed in tumors,. Even more, these structures can be induced in culture cells by overexpression of specific centrosomal proteins, such as CNap-1 or Nlp.These structures may look very similar, yet detailed studies reveal that they may present very different properties, depending on their proteic composition. For instance, their capacity to incorporate γ-TuRC complexes (see also: γ-tubulin) can be very variable, and so their capacity to nucleate microtubule
Microtubule
Microtubules are a component of the cytoskeleton. These rope-like polymers of tubulin can grow as long as 25 micrometers and are highly dynamic. The outer diameter of microtubule is about 25 nm. Microtubules are important for maintaining cell structure, providing platforms for intracellular...

s, therefore affecting in different way the shape, polarity and motility of implicated tumor cells.

Numeric aberrations

The presence of an inadecuate number of centrosomes is very often linked to the apparition of genome instability
Genome instability
Usually, all cells in an individual in a given species show a constant number of chromosomes, which constitute what is known as the karyotype defining this species , although some species present a very high karyotypic variability.Sometimes, in a species with a stable karyotype, random variations...

 and the loss of tissular differentiation. However, the method to count the centrosome number (each one with 2 centrioles) is often not very precise, because it is frequently assesed using fluorescence microscopy, whose resolution capacity is not the best. Nevertheless, it is clear that the presence of supernumerary (in excess) centrosomes is a common event in human tumors. It has been observed that loss of the tumor-suppressor protein p53
P53
p53 , is a tumor suppressor protein that in humans is encoded by the TP53 gene. p53 is crucial in multicellular organisms, where it regulates the cell cycle and, thus, functions as a tumor suppressor that is involved in preventing cancer...

 produces supernumerary centrosomes, as well as deregulation of other proteins implicated in tumorigenesis in humans, such as BRCA1
BRCA1
BRCA1 is a human caretaker gene that produces a protein called breast cancer type 1 susceptibility protein, responsible for repairing DNA. The first evidence for the existence of the gene was provided by the King laboratory at UC Berkeley in 1990...

 and BRCA2
BRCA2
BRCA2 is a protein that in humans is encoded by the BRCA2 gene.BRCA2 orthologs have been identified in most mammals for which complete genome data are available....

 (for references, see ). It is important to note that supernumerary centrosomes can be generated by very different mechanisms: specific reduplication of the centrosome, failure during cell division
Cell division
Cell division is the process by which a parent cell divides into two or more daughter cells . Cell division is usually a small segment of a larger cell cycle. This type of cell division in eukaryotes is known as mitosis, and leaves the daughter cell capable of dividing again. The corresponding sort...

 (generating an increase in chromosome number), cell fusion (for instance due to infection by specific viruses) or de novo generation of centrosomes. At this point there is not sufficient information to know how frequent are those mechanisms in vivo, but it is possible that the increase in centrosome numbers due a failure during cell division might be more frequent than appreciated, because many "primary" defects in one cell (deregulation of the cell cycle
Cell cycle
The cell cycle, or cell-division cycle, is the series of events that takes place in a cell leading to its division and duplication . In cells without a nucleus , the cell cycle occurs via a process termed binary fission...

, defective DNA
DNA
Deoxyribonucleic acid is a nucleic acid that contains the genetic instructions used in the development and functioning of all known living organisms . The DNA segments that carry this genetic information are called genes, but other DNA sequences have structural purposes, or are involved in...

 or chromatin
Chromatin
Chromatin is the combination of DNA and proteins that make up the contents of the nucleus of a cell. The primary functions of chromatin are; to package DNA into a smaller volume to fit in the cell, to strengthen the DNA to allow mitosis and meiosis and prevent DNA damage, and to control gene...

 metabolism, failure in the spindle checkpoint
Spindle checkpoint
In order to preserve one cell's identity and its proper functioning, it is necessary to maintain constant the appropriate number of chromosomes after each cell division...

, etc...) would generate a failure in cell division, an increase in ploidy
Ploidy
Ploidy is the number of sets of chromosomes in a biological cell.Human sex cells have one complete set of chromosomes from the male or female parent. Sex cells, also called gametes, combine to produce somatic cells. Somatic cells, therefore, have twice as many chromosomes. The haploid number is...

 and an increase in centrosome numbers as a "secondary" effect.

Evolution of the centrosome

The evolution
Evolution
Evolution is any change across successive generations in the heritable characteristics of biological populations. Evolutionary processes give rise to diversity at every level of biological organisation, including species, individual organisms and molecules such as DNA and proteins.Life on Earth...

ary history of the centrosome and the centriole
Centriole
A Centriole is a barrel-shaped cell structure found in most animal eukaryotic cells, though it is absent in higher plants and most fungi. The walls of each centriole are usually composed of nine triplets of microtubules...

 has been traced for some of the signature genes, e.g. the centrins. Centrins participate in calcium signaling
Calcium signaling
Calcium is a common signaling mechanism, as once it enters the cytoplasm it exerts allosteric regulatory effects on many enzymes and proteins...

 and are required for centriole duplication. There exist two main subfamilies of centrins, both of which are present in the early-branching eukaryote
Eukaryote
A eukaryote is an organism whose cells contain complex structures enclosed within membranes. Eukaryotes may more formally be referred to as the taxon Eukarya or Eukaryota. The defining membrane-bound structure that sets eukaryotic cells apart from prokaryotic cells is the nucleus, or nuclear...

 Giardia intestinalis. Centrins have therefore been present in the common ancestor of eukaryotes. Conversely, they have no recognizable homolog
Homology (biology)
Homology forms the basis of organization for comparative biology. In 1843, Richard Owen defined homology as "the same organ in different animals under every variety of form and function". Organs as different as a bat's wing, a seal's flipper, a cat's paw and a human hand have a common underlying...

s in archea and bacteria
Bacteria
Bacteria are a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria have a wide range of shapes, ranging from spheres to rods and spirals...

 and are thus part of the "eukaryotic signature genes." Although there are studies on the evolution of the centrins and centrioles, no studies have been published on the evolution of the pericentriolar material
Pericentriolar material
Pericentriolar material is an amorphous mass of protein which makes up the part of the centrosome that surrounds the two centrioles. The PCM contains proteins responsible for microtubule nucleation and anchoring including γ-tubulin, pericentrin and ninein....

.

It is evident that some parts of the centrosome are highly diverged in the model species Drosophila melanogaster
Drosophila melanogaster
Drosophila melanogaster is a species of Diptera, or the order of flies, in the family Drosophilidae. The species is known generally as the common fruit fly or vinegar fly. Starting from Charles W...

 and Caenorhabditis elegans
Caenorhabditis elegans
Caenorhabditis elegans is a free-living, transparent nematode , about 1 mm in length, which lives in temperate soil environments. Research into the molecular and developmental biology of C. elegans was begun in 1974 by Sydney Brenner and it has since been used extensively as a model...

. For example, both species have lost one of the centrin subfamilies that are usually associated with centriole duplication. Drosophila melanogaster mutants that lack centrosomes can even develop to morphologically normal adult flies, which then die shortly after birth because their sensory neurons lack cilia. Thus, these flies have evolved functionally redundant machinery, which is independent of the centrosomes.

Centrosome associated nucleotides

Research in 2006 indicated that centrosomes from Surf clam
Surf clam
The surf clam, Spisula solida, is a medium sized marine clam or bivalve mollusc. Up to 5 cm long, like many clams it is a sediment-burrowing filter feeder.This species of clam is found at scattered locations around the British and Irish coasts....

 eggs contain RNA
RNA
Ribonucleic acid , or RNA, is one of the three major macromolecules that are essential for all known forms of life....

 sequences. The sequences identified were found in "few to no" other places in the cell, and do not appear in existing genome
Genome
In modern molecular biology and genetics, the genome is the entirety of an organism's hereditary information. It is encoded either in DNA or, for many types of virus, in RNA. The genome includes both the genes and the non-coding sequences of the DNA/RNA....

 databases. One identified RNA sequence contains a putative RNA polymerase
RNA polymerase
RNA polymerase is an enzyme that produces RNA. In cells, RNAP is needed for constructing RNA chains from DNA genes as templates, a process called transcription. RNA polymerase enzymes are essential to life and are found in all organisms and many viruses...

, leading to the hypothesis of an RNA based genome within the centrosome. However, subsequent research has shown that centrosome do not contain their own DNA-based genomes. While it was confirmed that RNA molecules associate with centrosomes, the sequences have still been found within the nucleus. Furthermore, centrosomes can form de novo after having been removed (e.g. by laser irradiation) from normal cells.
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