Mitosis
From Wikipedia, the free encyclopedia
Mitosis is the process by which a cell separates its duplicated genome into two identical halves. It is generally followed immediately by cytokinesis which divides the cytoplasm and cell membrane. This results in two identical daughter cells with a roughly equal distribution of organelles and other cellular components. Mitosis and cytokinesis together is defined as the mitotic (M) phase of the cell cycle, the division of the mother cell into two daughter cells, each the genetic equivalent of the parent cell. Mitosis occurs exclusively in eukaryotic cells. In multicellular organisms, the somatic cells undergo mitosis, while germ cells — cells destined to become sperm in males or ova in females — divide by a related process called meiosis. Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.
The process of mitosis is complex and highly regulated. The sequence of events is divided into phases, corresponding to the competion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, telophase and anaphase. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell. The cell then divides in cytokinesis, to produce two identical daughter cells.
Because cytokinesis usually occurs in conjunction with mitosis, "mitosis" is often used interchangeably with "mitotic phase". However, there are many cells where mitosis and cytokinesis occur separately, forming single cells with multiple nuclei. This occurs most notably among the fungi and slime moulds, but is found in various different groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development.<ref name=Lilly>Lilly M, Duronio R (2005). "New insights into cell cycle control from the Drosophila endocycle.". Oncogene 24 (17): 2765-75. PMID 15838513.</ref> Errors in mitosis can either kill a cell through apoptosis or cause mutations that may lead to cancer.
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[edit] Overview
The primary result of mitosis is the division of the parent cell's genome into two daughter cells. The genome is composed of a number of chromosomes, complexes of tightly-coiled DNA that contain genetic information vital for proper cell function. Because each resultant daughter cell should be genetically identical to the parent cell, the parent cell must make a copy of each chromosome before mitosis. This occurs during the middle of interphase, the period that precedes the mitotic phase in the cell cycle where preparation for mitosis occurs.<ref name=Blow>Blow J, Tanaka T (2005). "The chromosome cycle: coordinating replication and segregation. Second in the cycles review series.". EMBO Rep 6 (11): 1028-34. PMID 16264427.</ref>
Each chromosome now contains two identical copies of itself, called sister chromatids, attached together in a specialized region of the chromosome known as the centromere. Each sister chromatid is not considered a chromosome in itself, and a chromosome does not always contain two sister chromatids.
In eukaryotes, the nuclear envelope that separates the DNA from the cytoplasm degrades, and its fluid spills out into the cytoplasm. The chromosomes align themselves in a line spanning the cell. Microtubules, essentially miniature strings, splay out from opposite ends of the cell and shorten, pulling apart the sister chromatids of each chromosome.<ref>Zhou J, Yao J, Joshi H (2002). "Attachment and tension in the spindle assembly checkpoint.". J Cell Sci 115 (Pt 18): 3547-55. PMID 12186941.</ref> As a matter of convention, each sister chromatid is now considered a chromosome, so they are renamed to sister chromosomes. As the cell elongates, corresponding sister chromosomes are pulled toward opposite ends. A new nuclear envelope forms around the separated sister chromosomes.
As mitosis completes cytokinesis is well underway. In animal cells, the cell pinches inward where the imaginary line used to be, separating the two developing nuclei. In plant cells, the daughter cells will construct a new dividing cell wall between each other. Eventually, the mother cell will be split in half, giving rise to two daughter cells, each with an equivalent and complete copy of the original genome.
Prokaryotic cells undergo a process similar to mitosis called binary fission. However, prokaryotes cannot be properly said to undergo mitosis because they lack a nucleus and only have a single chromosome with no centromere.<ref>Nanninga N (2001). "Cytokinesis in prokaryotes and eukaryotes: common principles and different solutions.". Microbiol Mol Biol Rev 65 (2): 319-33. PMID 11381104.</ref>
[edit] Phases
The mitotic phase is a relatively short action-packed period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for division. Interphase is divided into three phases, G1 (first growth), S (synthesis), and G2 (second growth). During all three phases, the cell grows by producing proteins and cytoplasmic organelles. However, chromosomes are replicated only during the S phase. Thus, a cell grows (G1), continues to grow as it duplicates its chromosomes (S), grows more and prepares for mitosis (G2), and divides (M).<ref name=Blow/>
Mitosis is a continual and dynamic process. For purposes of description, however, mitosis is conventionally broken down into five subphases: prophase, prometaphase, metaphase, anaphase, and telophase.
[edit] Prophase
Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin condenses together into a highly ordered structure called a chromosome. Since the genetic material has already been duplicated earlier in S phase, the replicated chromosomes have two sister chromatids, bound together at the centromere by the protein cohesin. Chromosomes are visible at high magnification through a light microscope.
Just outside the nucleus are two centrosomes. Each centrosome, which was replicated earlier independent of mitosis, acts as a coordinating center for the cell's microtubules. The two centrosomes sprout microtubules (which may be thought of as cellular ropes or poles) by polymerizing free-floating tubulin protein. By repulsive interaction of these microtubules with each other, the centrosomes push themselves to opposite ends of the cell (although new research has shown that there might be a mechanism inside the centromeres that also grab the microtubules and pull the chromatids apart). The network of microtubules is the beginning of the mitotic spindle.<ref>Rieder C (2005). "Kinetochore fiber formation in animal somatic cells: dueling mechanisms come to a draw.". Chromosoma 114 (5): 310-8. PMID 16270218.</ref>
Some centrosomes contain a pair of centrioles that may help organize microtubule assembly, but they are not essential to formation of the mitotic spindle.<ref>Lloyd C, Chan J. (2006). "Not so divided: the common basis of plant and animal cell division.". Nat Rev Mol Cell Biol. 7 (2): 147-52. PMID 16493420.</ref>
[edit] Prometaphase
The nuclear envelope dissolves and microtubules invade the nuclear space. This is called open mitosis, and it occurs in most multicellular organisms. Some protists, such as algae or trichomonads, undergo a variation called closed mitosis where the microtubules are able to penetrate an intact nuclear envelope.<ref>Heywood P. (1978). "Ultrastructure of mitosis in the chloromonadophycean alga Vacuolaria virescens.". J Cell Sci. 31: 37-51. PMID 670329.</ref><ref>Ribeiro K, Pereira-Neves A, Benchimol M (2002). "The mitotic spindle and associated membranes in the closed mitosis of trichomonads.". Biol Cell 94 (3): 157-72. PMID 12206655.</ref>
Each chromosome forms two kinetochores at the centromere, one attached at each chromatid. A kinetochore is a complex protein structure that is analogous to a ring for the microtubule hook; it is the point where microtubules attach themselves to the chromosome.<ref>Chan G, Liu S, Yen T (2005). "Kinetochore structure and function.". Trends Cell Biol 15 (11): 589-98. PMID 16214339.</ref> Although the kinetochore is not fully understood, it is known that it contains some form of molecular motor.<ref name=Maiato>Maiato H, DeLuca J, Salmon E, Earnshaw W (2004). "The dynamic kinetochore-microtubule interface.". J Cell Sci 117 (Pt 23): 5461-77. PMID 15509863.</ref> When a microtubule connects with the kinetochore, the motor activates, using energy from ATP to "crawl" up the tube toward the originating centrosome. This motor activity, coupled with polymerisation and depolymerisation of microtubules, provides the pulling force necessary to later separate the chromosome's two chromatids.<ref name=Maiato/>
When the spindle grows to sufficient length, kinetochore microtubules begin searching for kinetochores to attach to. A number of nonkinetochore microtubules find and interact with corresponding nonkinetochore microtubules from the opposite centrosome to form the mitotic spindle.<ref name=Winey>Winey M, Mamay C, O'Toole E, Mastronarde D, Giddings T, McDonald K, McIntosh J (1995). "Three-dimensional ultrastructural analysis of the Saccharomyces cerevisiae mitotic spindle.". J Cell Biol 129 (6): 1601-15. PMID 7790357.</ref> Prometaphase is sometimes considered part of prophase.
[edit] Metaphase
As microtubules find and attach to kinetochores in prometaphase, the centromeres of the chromosomes convene along the metaphase plate or equatorial plane, an imaginary line that is equidistant from the two centrosome poles.<ref name=Winey/> This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug of war between equally strong people. In certain types of cells, chromosomes do not line up at the metaphase plate and instead move back and forth between the poles randomly, only roughly lining up along the midline.
Because proper chromosome separation requires that every kinetochore be attached to a bundle of microtubules, it is thought that unattached kinetochores generate a signal to prevent premature progression to anaphase without all chromosomes being aligned. The signal creates the mitotic spindle checkpoint.<ref>Chan G, Yen T. "The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit.". Prog Cell Cycle Res 5: 431-9. PMID 14593737.</ref>
[edit] Anaphase
When every kinetochore is attached to a cluster of microtubules and the chromosomes have lined up along the metaphase plate, the cell proceeds to anaphase.
Two events then occur; First, the proteins that bind sister chromatids together are cleaved, allowing them to separate. These sister chromatids turned sister chromosomes are pulled apart by shortening kinetochore microtubules and toward the respective centrosomes to which they are attached. Next, the nonkinetochore microtubules elongate, pushing the centrosomes (and the set of chromosomes to which they are attached) apart to opposite ends of the cell.
These two stages are sometimes called early and late anaphase. At the end of anaphase, the cell has succeeded in separating identical copies of the genetic material into two distinct populations.
[edit] Telophase
Telophase is a reversal of prophase and prometaphase events. It "cleans up" the aftereffects of mitosis. At telophase, the nonkinetochore microtubules continue to lengthen, elongating the cell even more. Corresponding sister chromosomes attach at opposite ends of the cell. A new nuclear envelope, using fragments of the parent cell's nuclear membrane, forms around each set of separated sister chromosomes. Both sets of chromosomes, now surrounded by new nuclei, unfold back into chromatin.
[edit] Cytokinesis
Often (mistakenly) thought to be the same process as telophase, cytokinesis, if it is to occur, is usually well under way by this time. In animal cells, a cleavage furrow containing a contractile ring develops where the metaphase plate used to be, pinching off the separated nuclei.<ref>Glotzer M (2005). "The molecular requirements for cytokinesis.". Science 307 (5716): 1735-9. PMID 15774750.</ref> In both animal and plant cells, cell division is also driven by vesicles derived from the Golgi apparatus, which move along microtubules to the middle of the cell. In plants this structure coalesces into a cell plate that then develops into a cell wall, separating the two nuclei.<ref>Albertson R, Riggs B, Sullivan W (2005). "Membrane traffic: a driving force in cytokinesis.". Trends Cell Biol 15 (2): 92-101. PMID 15695096.</ref> Each daughter cell has a complete copy of the genome of its parent cell. Mitosis is complete.
[edit] Significance
The importance of mitosis is the maintenance of the chromosomal set; each cell formed receives chromosomes that are alike in composition and equal in number to the chromosomes of the parent cell. Transcription is generally believed to cease during mitosis, but epigenetic mechanisms such as bookmarking function during this stage of the cell cycle to ensure that the "memory" of which genes were active prior to entry into mitosis are transmitted to the daughter cells.<ref>Zhou G, Liu D, Liang C (2005). "Memory mechanisms of active transcription during cell division.". Bioessays 27 (12): 1239-45. PMID 16299763.</ref>
[edit] Consequences of errors
Although errors in mitosis are rare, the process may go wrong, especially during early cellular divisions in the zygote. Mitotic errors can be especially dangerous to the organism because future offspring from this parent cell will carry the same disorder.
In non-disjunction, a chromosome may fail to separate during anaphase. One daughter cell will receive both sister chromosomes and the other will receive none. This results in the former cell having three chromosomes coding for the same thing (two sisters and a homologue), a condition known as trisomy, and the latter cell having only one chromosome (the homologous chromosome), a condition known as monosomy. These cells are considered aneuploidic cells and these abnormal cells can cause cancer.<ref>Draviam V, Xie S, Sorger P (2004). "Chromosome segregation and genomic stability.". Curr Opin Genet Dev 14 (2): 120-5. PMID 15196457.</ref>
Mitosis is a traumatic process. The cell goes through dramatic changes in ultrastructure, its organelles disintegrate and reform in a matter of hours, and chromosomes are jostled constantly by probing microtubules. Occasionally, chromosomes may become damaged. An arm of the chromosome may be broken and the fragment lost, causing deletion. The fragment may incorrectly reattach to another, non-homologous chromosome, causing translocation. It may reattach to the original chromosome, but in reverse orientation, causing inversion. Or, it may be treated erroneously as a separate chromosome, causing chromosomal duplication. The effect of these genetic abnormalities depend on the specific nature of the error. It may range from no noticeable effect, cancer induction, or organism death.
[edit] Endomitosis
Endomitosis is a variant of mitosis without nuclear or cellular division, resulting in cells with many copies of the same chromosome occupying a single nucleus. This process may also be referred to as endoreduplication and the cells as endoploid.<ref name=Lilly/>
[edit] Timeline in pictures
Real mitotic cells can be visualized through the microscope by staining them with fluorescent antibodies and dyes. These light micrographs are included below.
Early prophase: Nonkinetochore microtubules, shown as green strands, have established a matrix around the degrading nucleus, in blue. The green nodules are the centrosomes. |
Early prometaphase: The nuclear membrane has just degraded, allowing the microtubules to quickly interact with the kinetochores on the chromosomes, which have just condensed. |
Early anaphase: The centrosomes have moved to the poles of the cell and have established the mitotic spindle. The chromosomes, in light blue, have been split by shortening kinetochore microtubules. |
Anaphase: Lengthening nonkinetochore microtubules push the two sets of chromosomes further apart. |
[edit] References
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[edit] Further reading
- Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P (2002). Mitosis. Molecular Biology of the Cell. Garland Science. Retrieved on January 22, 2006.
- Campbell, N. and Reece, J. (December 2001). “The Cell Cycle”, Biology, 6th ed., San Francisco: Benjamin Cummings/Addison-Wesley, pp. 217-224. ISBN 0-8053-6624-5.
- Cooper, G. (2000). The Events of M Phase. The Cell: A Molecular Approach. Sinaeur Associates, Inc. Retrieved on January 22, 2006.
- Freeman, S (2002). “Cell Division”, Biological Science. Upper Saddle River, NJ: Prentice Hall, pp. 155-174. ISBN 0-13-081923-9.
- Lodish H, Berk A, Zipursky L, Matsudaira P, Baltimore D, Darnell J (2000). Overview of the Cell Cycle and Its Control. Molecular Cell Biology. W.H. Freeman. Retrieved on January 22, 2006.
[edit] External links
- Science aid: Mitosis and meiosis: A simple account of the mitotic and meiotic processes.
- Mitosis Animations: A side-by-side animated explanation of the differences between meiosis and mitosis.
- Mitosis Animation: A great animation of mitosis.cs:Mitóza
da:Mitose de:Mitose es:Mitosis fr:Mitose it:Mitosi he:מיטוזה lt:Mitozė hu:Mitózis mk:Митоза nl:Mitose ja:体細胞分裂 pl:Mitoza pt:Mitose ru:Митоз simple:Mitosis sk:Mitóza sl:Mitoza sr:Митоза sv:Mitos [Mitosis animation]
