2009 Group 3 Project
- 1 Cell Division
- 1.1 Introduction
- 1.2 Types of Cell Division
- 1.3 History of Cell Division Research
- 1.4 Mechanisms of Cell Division
- 1.5 Current Research on Cell Division
- 1.6 Errors in Cell Division
- 1.7 Glossary of terms
- 1.8 References
- 1.9 2009 Group Projects
Cell Theory was fundamentally developed by Schwann and Schleiden (Mazarello, 1999). One of the three components states that cells are derived from pre-existing cells, which is demonstrated by the concept of cell division. In understanding cell division it is crucial to understand that cell division is merely a fragment of the Cell Cycle, ie M phase(Alberts et al, 2002). Cell division is the process by which a cell is able to replicate itself. There are essentially three different modes of cell division. The different types of division are present due to the different types of organisms, or the purpose of the cell. The three main differing types of Cell Division are Binary fission, Mitosis, and Meiosis.
Types of Cell Division
Binary Fission is the mode of cell division whereby prokaryotes(e.g, amoeba) duplicate themselves. It is a known type of asexual reproduction where the cell is divided in a way such that the product is equal to/almost equal to that of the original. The division of the cell includes the genetic material as well, however there is often a high mutation rate. Thus the high mutation rate enables bacteria to develop resistance to antibiotics and other drugs/chemicals.
Mitosis is a process of cell replication where the parent cell duplicates the DNA and then divides into two daughter cells which are almost or are equal to each other. It is replicated such that it remains a diploid cell. In introducing mitosis as a means by which cell division occurs, it essentially consists of 5 phases, such as prophase, prometaphase, metaphase, anaphase, and telophase(Alberts et al, 2002). After interphase(which consists of the rest of the phases of cell cycle, G1, S, S2, Alberts et al 2002) occurs, where the genetic material is replicated, the 2 sets of chromosomes/ 4 sister chromatids then become condensed and the nuclear envelope is then broken down and the sister chromatids are attached to the spindle and lined up in the centre. The chromatids are then pulled towards the poles and the nuclear envelopes reform and thus two identical daughter cells are the result.
Meiosis is a process of cell division, which is associated with gametogenesis. Gametogenesis is the formation of gametes by process of meiosis, whereby cells which are replicated, and diploid cells become haplpoid.It can described in two phases, reduction and division. Similar to mitosis, it follows a similar sequence of prophase, metaphase, anaphase, telophase, however, it is carried out twice. Meiosis is similar to mitosis in that the DNA replicates and the sister chromatids are condensed, and the nuclear envelope is broken, however, the chromatids do not line up in the middle and are not attached to the spindle, but instead are sent to either poles, where crossover may occur. The act of crossing over of chromatids, this allows for genetic variation. Two daughter cells are then produced with single sets of chromosomes, and the resulting daughter cells are now haploid, as opposed to the end products of mitosis which are two diploid cells that are identical to each other. Meiosis is also identified as being process by which a cell is replicated and reduced.
History of Cell Division Research
There have been various theories throughout history in the understanding of how new cells arise (Robinson, 2002). During the 1830s, there were two contradicting ideas. The first was an observation that new cells arise spontaneously from molecular materials, or from within old cells. The other theory was that cells are able to split themselves into two, in a process described as "binary fission".
The following is a timeline illustrating this development of ideas.
- 1832 - Barthelemy Dumortier (1797–1878) of France studied plant cells. He observed the formation of a mid-line partition between the original cell and the new cell, and described this as the process of "binary fission" (cell division). These observations led him to reject the idea that new cells arise from within old ones, or that they form spontaneously from noncellular material.
- 1838 - Matthais Schleiden (1804–1881) proposed that every structural element of plants is composed of cells or the products of cells. He thus insisted that cells arise by a crystallization-like process either within other cells or from outside.
- 1852 - Robert Remak (1852–1865) published his observations on cell division, stating that Schleiden was wrong. He based his study on embryos, which led him to conclude that binary fission was the means of reproduction of new animal cells. Remak, however, failed to publicize his view. Instead, it was Rudolf Virchow, another microbiologist, who publicized it under his own name. Virchow is thus commonly given credit for the phrase Omnis cellula e cellula, meaning "all cells from preexisting cells".
- 1879 Walther Flemming (1843–1905) coined the term "mitosis" in his study of salamander cells (Mitchison & Salmon, 2001). He noted that during mitosis, the chromosomes split longitudinally. Based on Flemming's discovery, Wilhelm Roux (1850–1924) proposed that each chromosome carried a different set of hereditable elements and suggested that the longitudinal splitting observed by Flemming ensured the equal division of these elements.
- 1902 - Theodor Boveri (1862–1915) confirmed Roux and Flemming's observations. He made discoveries on mitotic spindle division through the study of fertilised sea urchin eggs, and highlighted the central role of the chromosomes in carrying genetic material (Mitchison & Salmon, 2001).
Consequently of these important initial discoveries on the propagation of cells, cell biologist have been making more findings on specific mechanisms within the theory of cell division. One of the most significant discovery in the recent 20th Century is the double-helical structure of the DNA by James Watson and Francis Crick, which explains the mechanism of DNA replication. A timeline of other milestones in cell division research can be found here.
An important factor behind new research on cell division is the advance in imaging techniques. The inventions of the microscope, the electron microscope and various other technologies have aided with these discoveries, allowing scientists to observe the cell cycle with live imaging.
Mechanisms of Cell Division
Mitosis is the process of creating genetically identical daughter cells from a parent cell. This allows for accurate replication of DNA which is important in any organism. The DNA replicates and only divides once splitting into two daughter cells, unlike meiosis which replicates twice which creates 4 cells. The daughter cells produced by mitosis are called diploid as they contain 46 chromosomes whilst the haploid cells produced by meiosis only have 23 chromosomes and are gametes. There are several proteins which are involved in cell division, some controlling the entire cell cycle which controls the timeline of when things are to occur, while others allow cohesion of the chromatids, the breakdown of cohesion, and the motors that allow the mitotic spindle to draw the replicated chromosomes to opposite poles of the cell, and finally the protein that initiates cytokinesis. The main proteins involved in cell division are CDK-1, Cyclin B, Cyclin D, Cdk4, Cohesin, and Seperase. These proteins are crucial to the successful process of cell division.
- There are 5 phases for mitosis
- The mitotic spindle starts to attach to the Chromatids which are in no allignment at this time. The chromatids are then migrate to the centre of the cell and form into two lines on the equatorial line.
- Is marked by the disappearance of the nuclear envelope, chromosomes start to move towards the poles. ‘The chromosomes are still being held along the equatorial line by the mitotic spindle and cohesion holding the centromeres of the pairing of chromatids together’ (Purves, Sadava, Orians, Heller, 2004. pg 172).
- Is the condensing of the DNA and attached to the poles of the cell. ‘once all of the chromatids are attached to the poles by the mitotic spindle, seperase is used to catalyse cohesin breakdown’ (Purves at al, 2004. pg 173) allowing the chromatids to separate and move towards the opposite spindle poles.
- The separation of the sister chromatids to opposite poles is the beginning of the anaphase process. ‘The chromatids are now referred to as the daughter chromosomes’ (Purves et al, 2004, pg 173)
- The chromatids have now been drawn to opposite sides of the cell by the Mitotic spindle. This allows for cytokinesis to occur dividing the cell into two equal daughter cells. Cytokinesis is the last process of cell division. Cytokinesis is the process of microfilaments causing a furrow on the cell, which tightens until the cell membrane comes together, fuses causing two identical daughter cells. This process is different in plant cells as they have a cell wall, the idea is the same, but a ‘cell plate is created in the middle of the cell which elongates until the membrane reaches the cell wall and fuses, thus separating the cells’ (Purves et al, 2004, pg 174).
An online animation is available here to help visualise this process.
Meiosis is the process of reducing the number of chromosomes in a cell, which allows for diversity. Meiosis has 2 nuclear divisions that reduce the number chromosomes from diploid to haploid in preparation for sexual reproduction, the cells involved in meiosis are called gametes. In meiosis, the chromatids are allowed to diversify. When the chromatids synapse along the equatorial line, certain parts of the homologous chromatid will crossover with the pair homologous chromatid creating recombiant chromatids, crossover allows the diversification of the DNA. ‘The result of meiosis is 4 nuclei, each nucleus is haploid and has a single set of unreplicated chromosomes that differs from other sets in its genetic composition’ (Purves et al, 2004, pg 180). There are only 2 phases in the meiotic process, phase 1 is the synapse of the homolog chromatids along the equatorial line. Phase 2 is the separation of the homolog chromatids.
An online animated tutorial is available here for further interests.
The mechanical processes of Binary fission are poorly understood. It is known that binary fission uses asexual production. Bacterium do not have a nucleus. The cell is divided by cytokinesis which relies on the ftsZ protein. ‘In bacteria, the ftsZ gene product, FtsZ, is required for cell division, playing a prominent role in cytokinesis’ (de Boar, Crossley, Rothfield, 1992). De boar, Crossley and Rothfield state the ftsZ protein specifically binds GTP and hydrolises it. This is crucial as ‘GTP binding and hydrolysis are important in enabling FtsZ to support bacterial cytokinesis’ (deboar et al. 1992). Bacteria are able to proliferate rapidly due to binary fission. Due to the rapid divison process of Binary fission, several DNA mutations occur during the process (Lenski, Winkworth, Riley. 2002). These mutation may be harmless or harmful depending upon the mutation. Cairns, Overbaugh and Miller believe the 'mechanisms of the bacterium choose which DNA mutations will occur' (1988). The mechanisms of Binary fission are poorly understood and the speed of the devision process causes errors in the DNA coding.
Cytokinesis is the process of creating the 2 daughter cells. Cytokinesis is classified as being just after the mitotic phase, so is not included but is included in Meiotic phase. Cytokinesis is the production of a microfilament ring which is placed under the membrane in the midpoint of the cell. The ring then contracts creating a furrow which deepens eventually causing the membrane to pinch creating two separate cells called daughter cells which have divided the contents of the cytoplasm evenly.
- organelles of the cytoplasm which are divided into the 2 daughter cells
- Golgi apparatus
- Mitotic spindle
The mitotic spindle is a major part of the cell division process. It draws the sister chromatids to opposite sides of the cell, towards the mitotic spindle poles. There are two mitotic spindles per mother cell. Each one pulls a row of chromosomes towards its pole. The sister chromatids are held together by the protein cohesin which has to be catalysed by separase. This separates the chromosomes allowing for the mitotic spindles to draw the sister chromosomes apart, allowing for cytokinesis to occur.
Proteins of Cell Division
- Cell division cycle 2 (CDK1) induces entry into M phase and is found in all eukaryotes(Linqvist et al, 2007)
- Cyclin B
- Cyclin B forms part of the Mitosis Promoting Factor (MPF) and is crucial to nuclear translocation(Alberts et al, 2002)
- Cyclin D
- Cyclin D provides a DNA binding site
- Cdk4 is pivotal in controlling cell proliferation in the G1 phase
- This protein holds the chromatids together in both mitosis and meiosis. It allows for the replication of DNA to occur as accurately as possible (Díaz-Martínez et al, 2007)
- This protein, also known as Anaphase promoting complex (APC), acts after the DNA has been accurately replicated and allows the daughter chromosomes to separate and move to the opposite poles of the cell. Seperase works by catalysing the cohesin, degrading it, thus separating the sister chromatids. APC also degrades other mitotic CDK complexes rsulting in the completion of the mitotic process. http://www.ncbi.nlm.nih.gov/books/bookres.fcgi/mcb/ch24anim1.mov
- regulate the microtubule attachment at the kinetochores and also the tension between sister kinetochores. Also activation of the spindle assembly checkpoint (SAC) to delay the mitotic process when either of these is absent.
Current Research on Cell Division
The activity of the spindle assembly checkpoint (SAC) within dividing cells has been observed in the absence of the normally occurring tension between sister kinetochores of neighbouring chromosomes. The SAC within a cell usually monitors both the attachment of kinetochores to their corresponding kinetochore microtubules and the stretch between the centromeres of sister chromosomes which provides tension. This feat was achieved through the use of cells undergoing mitosis with unreplicated genomes (MUG), and therefore with kinetochores non-existent, hence no active tension at the centromeres. This suggests SAC and thus mitosis can occur without any interkinetochore tension present. (O Connell et al, 2008)
The rate of Nuclear Envelope (NE) formation was found to be limited by the chromatin-mediated reshaping of the endoplasmic reticulum (ER). Time lapse microscopy was used to quantatively analyse the nuclear membrane assembly within the mitotic metazoan cells. The over-expression of proteins involved in the forming of ER tubules resulted in the inhibition of nuclear expansion and NE formation. This suggests that the reorganisation of tubular ER is limiting the rate of NE assembly, with evidence also suggesting the proteins involved in ER modelling also play a part in NE formation as a principal component of the NE is ER creation.
Errors in Cell Division
- There are 3 main types of errors in cell division. They are:
- Error in the division process. Examples of such diseases where this has taken place are Down syndrome, Triple-X syndrome, Klinefelter's Syndrome, and Turner's Syndrome.
- Is a ‘condition in which one of the chromosomes are either lacking or present in excess’ (Purves et al, 2004, pg 182), one of the reasons could be the cohesin protein being absent or in excess. Anaeuploidy can be found in both the mitotic and meiotic processes. It can be expressed as monosomy (the lack of 1 chromosome), disomy (presence of 2 copies), trisomy(presence of an extra chromosome), tetrasomy (the presence of 2 extra chromosomes) and pentasomy (presence of 3 extra chromosomes). Example of aneuploidy are tumours, Down Syndrome (trisomy 21) etc. Click here for a detailed explanation of aneuploidy.
- In meiotic process where the crossing over does not occur in an equal manner, causing one chromatid to become longer or smaller than its pair, this usually occurs because one part of a chromatid has broken off and attached to another chromatid.
Glossary of terms
- Centromere - The region where sister chromatids join.
- Chromatid - One single-strand of chromosome from the newly replicated sister chromosomes, only recognised as so after the S-phase and before anaphase, with centromeres still intact.
- Chromosome - The DNA, and protein(eukaryotes), structure found within a cell that holds its genetic information.
- Cytokinesis - The process of the division of the cytoplasm in a dividing cell, which takes place after mitosis and completes the cell cycle.
- Eukaryote - Organisms whose cells contain a nucleus which stores its genetic make-up.
- Kinetochore - The protein structure found on chromosomes which is the site of attachment of the mitotic spindles (microtubules) allowing the separation of chromosomes to occur.
- Meiosis - The process where 4 haploid daughter cells(gametes) are formed through the division of a diploid mother cell.
- Mitosis - A type of cell division in which a single cell divides into two; each resulting cell has the same amount of chromosomes and genetic content as the original cell.
- Prokaryote - Organisms whose cells do not contain a nucleus and thus whose genetic make-up is stored freely in the cells. e.g. bacteria and archaea.
- Alberts B; Johnson A; Lewis J; Raff M; Roberts K; Walter P, Molecular Biology of the Cell, New York and London: Garland Science; c2002
- Cairns J, Overbaugh J, Miller S. 1988. The origin of mutants. Nature. 335:142
- de Boar P, Crossley R, Rothfield L. 1992. The essential bacterial cell-division protein FtsZ is a GTPase. Nature. 359(6392):254-6
- Díaz-Martínez LA, Giménez-Abián JF, Clarke DJ, 2007 Cohesin Is Dispensable for Centromere Cohesion in Human Cells. PLoS ONE 2(3): e318. doi:10.1371/journal.pone.0000318
- Erich A. Nigg, 2001, Mitotic kinases as regulators of cell division and its checkpoints, Nature Reviews Molecular Cell Biology 2, 21-32 (January 2001) | doi:10.1038/35048096
- Lenski RE, Winkworth CL, Riley MA. 2002. Rates of DNA sequence Evolution in experimental populations of escherichia coli during 20,000 generations. Journal of molecular evolution. 56(4):498-508
- The Internet Encyclopedia of Science, http://www.daviddarling.info/encyclopedia/B/binary_fission.html, Accessed: 25/04/09
- The Internet Encyclopedia of Science, http://www.estrellamountain.edu/faculty/farabee/biobk/BioBookmeiosis.html, Accessed: 01/05/09
- The Internet Encyclopedia of Science, http://www.daviddarling.info/encyclopedia/M/mitosis.html, Accessed: 30/04/09
- Lindqvist A, van Zon W, Karlsson Rosenthal C, Wolthuis RMF (2007) Cyclin B1–Cdk1 Activation Continues after Centrosome Separation to Control Mitotic Progression. PLoS Biol 5(5): e123. doi:10.1371/journal.pbio.0050123
- Mazarello P, (1999), A unifying concept: the history of cell theory, Nature Cell Biology 1, E13 - E15, doi:10.1038/8964
- Mitchison T.J. and Salmon E.D. (2001) 'Mitosis: a history of division', Nature Cell Biology, 3, pp 17-21. Retrieved from http://www.nature.com/celldivision/library/articles/ncb0101_e17/ncb0101_e17.html.
- Nature Publishing Group, Web Focus on Cell Division, A specially written series of short articles on
the main discoveries that have shaped the field of cell division
- Purves W.K, Sadava D, Orians G.H, Heller H.C (2004) Life: The Science of Biology 7th edition. Sinauer associates and VHPS/W.H. Frreman & Co.
- Ratogi, C.S.,(2003) Cell and Moelcular Biology, New Age International.
- Robinson, R. (2002). 'History of Biology: Cell Theory and Cell Structure', Gale Group. Retrieved from http://www.encyclopedia.com/doc/1G2-3400700213.html.
2009 Group Projects
--Mark Hill 14:02, 19 March 2009 (EST) Please leave these links to all group projects at the bottom of your project page.
Group 1 Meiosis | Group 2 Cell Death - Apoptosis | Group 3 Cell Division | Group 4 Trk Receptors | Group 5 The Cell Cycle | Group 6 Golgi Apparatus | Group 7 Mitochondria | Group 8 Cell Death - Necrosis | Group 9 Nucleus | Group 10 Cell Shape