Mitosis

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Mitosis in an animal cell.
Mitosis divides the chromosomes in a cell nucleus.
Onion (Allium) cells in different phases of the cell cycle, some in mitosis.
Time-lapse video of mitosis in a Drosophila melanogaster embryo.

Mitosis is the process, in the cell cycle, by which a cell duplicates into two genetically alike (identical) daughter cells. In mitosis, chromosomes in the cell nucleus are separated into two identical sets of chromosomes, each in its own nucleus. In general, mitosis is followed immediately by cytokinesis, which divides the cytoplasm, organelles, and cell membrane, and later karyokinesis, which divides the nucleus, dividing cell into two containing roughly equal shares of these cellular components.[1] Mitosis and cytokinesis together define the mitotic (M) phase of the cell cycle—the division of the mother cell into two daughter cells, genetically identical to each other and to their parent cell. This accounts for approximately 20% of the cell cycle.

Mitosis occurs only in eukaryotic cells and the process varies in different groups.[2] For example, animals undergo an "open" mitosis, where the nuclear envelope breaks down before the chromosomes separate, while fungi such as Aspergillus nidulans and Saccharomyces cerevisiae (yeast) undergo a "closed" mitosis, where chromosomes divide within an intact cell nucleus.[3] Prokaryotic cells, which lack a nucleus, divide by a process called binary fission.

The process of mitosis is fast and highly complex. The sequence of events is divided into stages corresponding to the completion of one set of activities and the start of the next. These stages are prophase, prometaphase, metaphase, anaphase, and telophase. During mitosis, the pairs of chromatids 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 daughter cells.[4]

Because cytokinesis often 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. The most notable occurrence of this is among the fungi and slime molds, but is found in various groups. Even in animals, cytokinesis and mitosis may occur independently, for instance during certain stages of fruit fly embryonic development.[5] Errors in mitosis can either kill a cell through apoptosis or cause mutations. Certain types of cancer can arise from such mutations.

Mitosis was discovered in frog, rabbit, and cat cornea cells in 1873 and described for the first time by the Polish histologist Wacław Mayzel in 1875.[6][7] The term is derived from the Greek word μίτος mitos "warp thread".[8][9]

Overview of cell cycle in relation to mitosis[edit]

The primary result of mitosis is the transferring of the parent cell's genome into two daughter cells. These two cells are identical and do not differ in any way. 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 chromatid before mitosis. This occurs during the S phase of interphase, the period that precedes the mitotic phase in the cell cycle where preparation for mitosis occurs.[10]

The two identical chromatids resulting from chromatid duplication are called sister chromatids. They are held together by a specialized region of the chromosome: a DNA sequence called the centromere.

Mitosis begins when the chromosomes condense and become visible. In most eukaryotes, the nuclear membrane, which segregates the DNA from the cytoplasm, disintegrates into membrane vesicles. The nucleolus, which makes ribosomes in the cell, also dissolves. The chromosomes align themselves in a line spanning the cell. Microtubules—in essence, miniature strings—splay out from opposite ends of the cell and shorten, pulling apart the sister chromatids of each chromosome.[11] Sister chromatids at this point are called daughter chromosomes. As the cell elongates, corresponding daughter chromosomes are pulled toward opposite ends. A new nuclear membrane forms around the separated daughter chromosomes.

As mitosis completes, the cell begins cytokinesis. In animal cells, the cell pinches inward where the imaginary line used to be (the area of the cell membrane that pinches to form the two daughter cells is called the cleavage furrow), separating the two developing nuclei. In plant cells, the daughter cells will construct a dividing cell wall. Eventually, the parent cell will be split in half, giving rise to two daughter cells, each with a replica of the original genome.

Prokaryotic cells undergo a process called binary fission, which is very much different from the process of mitosis, because there are no nuclear dynamics and chromosomes aren't linear.[12][clarification needed]

Phases of cell cycle and mitosis[edit]

Interphase[edit]

The cell cycle

The mitotic phase is a relatively short period of the cell cycle. It alternates with the much longer interphase, where the cell prepares itself for the process of cell division. Interphase is divided into three phases: G1 (first gap), S (synthesis), and G2 (second gap). 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 finally it divides (M) before restarting the cycle.[10] All these phases in the cell cycle are highly regulated, mainly via proteins. The phases follow one another in strict order and there are "checkpoints" that give the cell the cues to proceed from one phase to another. There is also a fourth section in Interphase where the cell has the option to enter G0. Cells continue on through this cell cycle until they become too crowded; at that point they will exit the cell cycle and enter G0. This reaction is called contact inhibition or density-dependent inhibition. Altogether interphase takes up roughly 90% of a cell's lifespan.

Preprophase (Plant Cells)[edit]

In plant cells only, prophase is preceded by a pre-prophase stage. In highly vacuolated plant cells, the nucleus has to migrate into the center of the cell before mitosis can begin. This is achieved through the formation of a phragmosome, a transverse sheet of cytoplasm that bisects the cell along the future plane of cell division. In addition to phragmosome formation, preprophase is characterized by the formation of a ring of microtubules and actin filaments (called preprophase band) underneath the plasma membrane around the equatorial plane of the future mitotic spindle. This band marks the position where the cell will eventually divide. The cells of higher plants (such as the flowering plants) lack centrioles; instead, microtubules form a spindle on the surface of the nucleus and are then organized into a spindle by the chromosomes themselves, after the nuclear membrane dissolves.[13] The preprophase band disappears during nuclear membrane dissolution and spindle formation in prometaphase.[14]

Prophase: The two round objects above the nucleus are the centrosomes. The chromatin is condensing into chromosomes. 
Prometaphase: The nuclear membrane disintegrates, and microtubules have invaded the nuclear space. These microtubules can attach to kinetochores or they can interact with opposing microtubules. 
Metaphase: The chromosomes align at the metaphase plate. 
Anaphase: The chromosomes split and the kinetochore microtubules shorten. 
Telophase: The decondensing chromosomes are surrounded by nuclear membranes. Cytokinesis has already begun; the pinched area is known as the cleavage furrow

Prophase[edit]

Condensing chromosomes. Interphase nucleus (left), condensing chromosomes (middle) and condensed chromosomes (right).

During this stage the cell prepares to divide by dissolving the membrane around the nucleus and the chromatin condenses into chromosomes. Normally, the genetic material in the nucleus is in a loosely bundled coil called chromatin. At the onset of prophase, chromatin fibers become tightly coiled, condensing into discrete chromosomes. It is crucial for the reader to note that chromatin is a complex consisting of both DNA and specific proteins. 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 cohesin protein complex. Chromosomes are typically visible at high magnification through a light microscope.

Also inside the nucleus, the nucleolus in the nucleus disappears from view. This is noteworthy because the cell does not need to divide the nucleolus right away. It will later reform when the nucleus divides completely.

Close to the nucleus are structures called centrosomes, consisting of a pair of centrioles, and actin, a halo of microtubule fragments. Centrioles are found in most eukaryotic animal cells. The centrosome is the coordinating center for the cell's microtubules. A cell inherits a single centrosome at cell division, which is replicated by the cell with the help of the nucleus before a new mitosis begins, giving a pair of centrosomes. The two centrosomes nucleate microtubules (which may be thought of as cellular ropes or poles) to form the spindle by polymerizing soluble tubulin. Molecular motor proteins then push the centrosomes along these microtubules to opposite sides of the cell. Although centrioles help organize microtubule assembly, they are not essential for the formation of the spindle, since they are absent from plants,[13] and centrosomes are not always used in mitosis.[15]

Prometaphase[edit]

Note: Prometaphase is sometimes included as part of the end of prophase or part of early metaphase.

During early prometaphase, the nuclear membrane disintegrates and microtubules invade the nuclear space. This is called open mitosis, and it occurs in most multicellular organisms. Fungi and some protists, such as algae or trichomonads, undergo a variation called closed mitosis where the spindle forms inside the nucleus, or its microtubules are able to penetrate an intact nuclear membrane, which stays intact.[16][17]

In late prometaphase, each chromosome forms two kinetochores at its 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.[18] Although the kinetochore structure and function are not fully understood, it is known that it contains some form of molecular motor.[19] 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.[19]

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.[20]

In the fishing pole analogy, the kinetochore would be the "hook" that catches a sister chromatid or "fish". The centrosome acts as the "reel" that draws in the spindle fibers or "fishing line". It is also one of the main phases of mitosis because without it cytokinesis would not be able to occur.

Metaphase[edit]

A cell in late metaphase. All chromosomes (blue) but one have arrived at the metaphase plate.

Metaphase came from the Greek word μετα meaning "after." After the microtubules have found and attached to the kinetochores in prometaphase,[21] the two centrosomes start pulling the chromosomes through their attached centromeres towards the two ends of the cell. As a result, the chromosomes come under longitudinal tension from the two ends of the cell. The centromeres of the chromosomes, in some sense, convene along the metaphase plate or equatorial plane, an imaginary line that is right in between the two centrosome poles.[20] This line is called the spindle equator. This even alignment is due to the counterbalance of the pulling powers generated by the opposing kinetochores, analogous to a tug-of-war between people of equal strength. 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 (spindle fibres), 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.[22]

Anaphase[edit]

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 (from the Greek word ανα meaning "up," "against," "back," or "re-").

Two events then occur: First, the proteins that bind sister chromatids together are cleaved. These sister chromatids now become separate daughter chromosomes, and are pulled apart by shortening kinetochore microtubules and move toward the respective centrosomes to which they are attached. The cleaved centromeres go first while the chromatids trail behind. They all look as if they are trying to grab at their partners, because they become shaped like a V.

Next, the polar microtubules elongate, pulling the centrosomes (and the set of chromosomes to which they are attached) apart to opposite ends of the cell. The force that causes the centrosomes to move toward the ends of the cell is still unknown, although there is a theory that suggests that the rapid assembly and breakdown of microtubules may cause this movement. At the end of anaphase the kinetochore microtubules all degrade.[23]

Telophase[edit]

Telophase (from the Greek word τελος meaning "end") is a reversal of prophase and prometaphase events. It "cleans up" the after effects of mitosis. At telophase, the polar microtubules continue to lengthen, elongating the cell even more. Corresponding daughter chromosomes attach at opposite ends of the cell. A new nuclear membrane, using the membrane vesicles of the parent cell's old nuclear membrane, forms around each set of separated daughter chromosomes (though the membrane does not enclose the centrosomes) and the nucleolus reappears. Both sets of chromosomes, now surrounded by new nuclei, begin to "relax" or decondense back into chromatin. Mitosis is complete, but cell division is not.

Cytokinesis[edit]

Cilliate undergoing cytokinesis, with the cleavage furrow being clearly visible

Cytokinesis is often mistakenly thought to be the final part of telophase; however, cytokinesis is a separate process that begins at the same time as telophase. Cytokinesis is not, in the technical sense, even a phase of mitosis but rather a separate process, necessary for completing cell division. In animal cells, a cleavage furrow (pinch) containing a contractile ring develops where the metaphase plate used to be, pinching off the separated nuclei.[24] 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.[25] In plants, this structure coalesces into a cell plate at the center of the phragmoplast and develops into a cell wall, separating the two nuclei. The phragmoplast is a microtubule structure typical for higher plants, whereas some green algae use a phycoplast microtubule array during cytokinesis.[26] Each daughter cell has a complete copy of the genome of its parent cell. The end of cytokinesis marks the end of the M-phase.

Significance[edit]

Mitosis is important for 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.

Mitosis occurs in the following circumstances:

Development and growth
The number of cells within an organism increases by mitosis. This is the basis of the development of a multicellular body from a single cell, i.e., zygote and also the basis of the growth of a multicellular body.
Cell replacement
In some parts of body, e.g. skin and digestive tract, cells are constantly sloughed off and replaced by new ones. New cells are formed by mitosis and so are exact copies of the cells being replaced. In like manner, RBCs (red blood cells) have short lifespan (only about 4 months) and new RBCs are formed by mitosis.
Regeneration
Some organisms can regenerate body parts. The production of new cells in such instances is achieved by mitosis. For example, starfish regenerate lost arms through mitosis.
Asexual reproduction
Some organisms produce genetically similar offspring through asexual reproduction. For example, the hydra reproduces asexually by budding. The cells at the surface of hydra undergo mitosis and form a mass called a bud. Mitosis continues in the cells of the bud and this grows into a new individual. The same division happens during asexual reproduction or vegetative propagation in plants.

Consequences of errors[edit]

An abnormal (tripolar) mitosis (12 o'clock position) in a precancerous lesion of the stomach. H&E stain

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 nondisjunction, 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 containing the same genes (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 aneuploid, a condition often associated with cancer.[27] On occasion when cells experience nondisjunction, they fail to complete cell division and retain both nuclei in one cell, resulting in binucleated cells.[citation needed]

Mitosis is a demanding process for the cell, which 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 depends on the specific nature of the error.[citation needed]

Endomitosis[edit]

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.[5] An example of a cell that goes through endomitosis is the megakaryocyte.[28]

Timeline in pictures[edit]

Real mitotic cells can be visualized through the microscope by staining them with fluorescent antibodies and dyes. These light micrographs are included below.

[29]

See also[edit]

References[edit]

  1. ^ "Mitosis". 
  2. ^ Raikov, I. B., 1994: The diversity of forms of mitosis in protozoa: a comparative review. European Journal of Protistology 30(3): 253-269.
  3. ^ De Souza CP, Osmani SA. (2007). "Mitosis, Not Just Open or Closed". Eukaryotic Cell 6 (9): 1521–7. doi:10.1128/EC.00178-07. PMC 2043359. PMID 17660363. 
  4. ^ Maton A, Hopkins JJ, LaHart S, Quon Warner D, Wright M, Jill D. (1997). Cells: Building Blocks of Life. New Jersey: Prentice Hall. pp. 70–4. ISBN 0-13-423476-6. 
  5. ^ a b Lilly M, Duronio R. (2005). "New insights into cell cycle control from the Drosophila endocycle". Oncogene 24 (17): 2765–75. doi:10.1038/sj.onc.1208610. PMID 15838513. 
  6. ^ Janusz Komender (2008). "Kilka słów o doktorze Wacławie Mayzlu i jego odkryciu". Postępy Biologii Komórki (Polskie Towarzystwo Anatomiczne, Polskie Towarzystwo Biologii Komórki) 35 (3): 405–407. 
  7. ^ Iłowiecki, Maciej (1981). Dzieje nauki polskiej. Warszawa: Wydawnictwo Interpress. p. 187. ISBN 83-223-1876-6. 
  8. ^ "mitosis". Online Etymology Dictionary. 
  9. ^ μίτος. Liddell, Henry George; Scott, Robert; A Greek–English Lexicon at the Perseus Project
  10. ^ a b Blow J, Tanaka T. (2005). "The chromosome cycle: coordinating replication and segregation: Second in the cycles review series". EMBO Rep 6 (11): 1028–34. doi:10.1038/sj.embor.7400557. PMC 1371039. PMID 16264427. 
  11. ^ Zhou J, Yao J, Joshi H. (2002). "Attachment and tension in the spindle assembly checkpoint". Journal of Cell Science 115 (Pt 18): 3547–55. doi:10.1242/jcs.00029. PMID 12186941. 
  12. ^ Nanninga N. (2001). "Cytokinesis in Prokaryotes and Eukaryotes: Common Principles and Different Solutions". Microbiology and Molecular Biology Reviews 65 (2): 319–33. doi:10.1128/MMBR.65.2.319-333.2001. PMC 99029. PMID 11381104. 
  13. ^ a b Lloyd C, Chan J. (2006). "Not so divided: the common basis of plant and animal cell division". Nature reviews. Molecular cell biology 7 (2): 147–52. doi:10.1038/nrm1831. PMID 16493420. 
  14. ^ Raven et al., 2005, pp. 58–67.
  15. ^ Varmark H (2004). "Functional role of centrosomes in spindle assembly and organization". Journal of Cellular Biochemistry 91 (5): 904–14. doi:10.1002/jcb.20013. PMID 15034926. 
  16. ^ Heywood P. (1978). "Ultrastructure of mitosis in the chloromonadophycean alga Vacuolaria virescens". Journal of Cell Science 31: 37–51. PMID 670329. 
  17. ^ Ribeiro K, Pereira-Neves A, Benchimol M. (2002). "The mitotic spindle and associated membranes in the closed mitosis of trichomonads". Biology of the Cell 94 (3): 157–72. doi:10.1016/S0248-4900(02)01191-7. PMID 12206655. 
  18. ^ Chan G, Liu S, Yen T. (2005). "Kinetochore structure and function". Trends in Cell Biology 15 (11): 589–98. doi:10.1016/j.tcb.2005.09.010. PMID 16214339. 
  19. ^ a b Maiato H, DeLuca J, Salmon E, Earnshaw W. (2004). "The dynamic kinetochore-microtubule interface". Journal of Cell Science 117 (Pt 23): 5461–77. doi:10.1242/jcs.01536. PMID 15509863. 
  20. ^ a b 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". Journal of Cell Biology 129 (6): 1601–15. doi:10.1083/jcb.129.6.1601. PMC 2291174. PMID 7790357. 
  21. ^ "The Cell Cycle & Mitosis Tutorial". University of Arizona. Retrieved 7 December 2012. 
  22. ^ Chan G, Yen T. (2003). "The mitotic checkpoint: a signaling pathway that allows a single unattached kinetochore to inhibit mitotic exit". Progress in Cell Cycle Research 5: 431–9. PMID 14593737. 
  23. ^ Miller KR. (2000). "Anaphase". Biology (5 ed.). Pearson Prentice Hall. pp. 169–70. ISBN 978-0-13-436265-6. 
  24. ^ Glotzer M. (2005). "The molecular requirements for cytokinesis". Science 307 (5716): 1735–9. doi:10.1126/science.1096896. PMID 15774750. 
  25. ^ Albertson R, Riggs B, Sullivan W. (2005). "Membrane traffic: a driving force in cytokinesis". Trends in Cell Biology 15 (2): 92–101. doi:10.1016/j.tcb.2004.12.008. PMID 15695096. 
  26. ^ Raven et al., 2005, pp. 64–7, 328–9.
  27. ^ Draviam V, Xie S, Sorger P. (2004). "Chromosome segregation and genomic stability". Current Opinion in Genetics & Development 14 (2): 120–5. doi:10.1016/j.gde.2004.02.007. PMID 15196457. 
  28. ^ Italiano JE, Shivdasani RA. (2003). "Megakaryocytes and beyond: the birth of platelets". Journal of Thrombosis and Haemostasis 1 (6): 1174–82. doi:10.1046/j.1538-7836.2003.00290.x. PMID 12871316. 
  29. ^ Carter, C.F. and Williamson, D.B. (2008) A rediscovered UK desmid: Closterium regulare Breb The Phycologist. Autumn 2008 No.75:24

Cited texts[edit]

  • Raven PH, Evert RF, Eichhorn SE. (2005). Biology of Plants (7th ed.). New York: W.H. Freeman and Company Publishers. ISBN 0-7167-1007-2. 

Further reading[edit]

  • Morgan, David L. (2007). The cell cycle: principles of control. London: Published by New Science Press in association with Oxford University Press. ISBN 0-9539181-2-2. 
  • Alberts B, Johnson A, Lewis J, Raff M, Roberts K, and Walter P (2002). "Mitosis". Molecular Biology of the Cell. Garland Science. Retrieved 2006-01-22. 
  • 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 2006-01-22. 
  • 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 2006-01-22. 

External links[edit]