Butschli suggested in 1876 that cell division comes about as a result of an increase in surface tension, prior to nuclear division, in the equatorial region of the cell. According to him, it is pre-requisite for substances streaming from the centrosomes to peak in concentration in the equatorial plane making it seem like these substances upregulates the surface tension of the cell with the most marked increase occurring at the equatorial region (Leach, Shenolikar, & Brautigan, 2013). This by his assertion will render the surface tension at the poles lower than at the equator.Today, we know that for Butschli’s assertion of cell division to hold, will mean that there should be streaming of materials towards the equator while the surface of the equator would have to be highly curved with relatively curved edge and equatorial surfaces highly flattened. If this were true, the result of the process would have been the formation of a flattened disc with a highly curved edge with the latter representing what was the equatorial surface of the edge prior to the process. Rather than what would have occurred in Butschli’s description, it is evident that cell division is the production of two spheres from one of approximately twice the volume of each of the two spheres referred to as daughter-cells. The relevant information herein is that cell division is an increase in surface which consequently diminishes surface tension rather than increasing it which was experimentally illustrated by Quincke. In this paper however, significant attention shall be given to the mechanics of cell division and how it influences the cell cycle and programmed cell deathCell is the basic functional unit of life. This presupposes that all activities that occur at the organismal level is a combined activities of similar cells. As these cellular activities occur, old cells lose their viability and would need to be replaced. The process through which this phenomenon, replacing less viable cells with newer ones, is achieved through cell division which is thrown into predetermined mechanics called phases. It is also worth stating that the growth of a single fertilized egg into a matured organism, replacement of dead tissues and diseases like cancer are all possible through this phenomenon. The cell cycle is made up of an ordered series of macroolucular proceedings that lead to mitosis, formation of two daughter cells. Each one of the cells produced containing chromosomes indistinguishable to those of the cell from which it was made alternatively known as parental cell. Doubling the parental chromosomes happens during the S phase of the cycle, with one of the produced daughter chromosomes distributed to each daughter cell at the time that the cell wall is splitting (cytokinesis) (see Figure 9-3). In order to ensure that duplication of chromosomes and their isolation to daughter cells occur in a predetermined order, and with extremely high fidelity, there is clear-cut temporal control of the events inherent in the cell cycle. It must also be noted that regulating the cell cycle is pivotal in order to ensure typical development of organisms of multiple cells. This also means that in an event where there is loss of control cancer, a diseases known to in developed world to kill one in every six, ensues. Somewhere In the late 1980s, it was determined that the molecular procedures which regulate the two important events in the cell cycle, chromosome copying and separation, are basically similar in all nuclei containing cells. This outstanding discovery served as a springboard for research with diverse organisms, with each of these organisms offering its own experimental advantages, in order to contribute the growing understanding how events in the cell cycle are coordinated and structured. Several techniques and procedures such as Biochemical and genetic experiments, coupled with recombinant DNA technology, have been devised to allow for studies in various aspects of the eukaryotic cell cycle. These studies have made profound discoveries, including that cell replication is primarily checked by regulating the timing of nuclear DNA copying and mitosis. The chief regulators of the events of the eukaryotic cell cycle are the heterodimeric protein kinases that comprises a regulatory subunit (cyclin) and catalytic subunit (cyclin dependent kinase). These kinases check the events of several proteins involved in DNA replication and mitosis specific regulatory sites phosphorylation. This strategic phosphorylation activate some and/or inhibit varieties of proteins to coordinate their activities. Cell cycle leads to cell replicationAs illustrated in Figure 21-1, The cell cycle is thrown into four distinct and predetermined major phases. In replication of somatic cells, cells make RNAs and proteins during the G1 phase, in waiting for DNA synthesis and chromosome duplication at the synthesis phase. After succeeding through the G2 phase, cells kick starts the rigorous and complex process known as mitosis, also called the M phase or mitotic phase. Even though the mitotic phase is part or the bigger process, cell cycle, it is also in itself divided into several stages (see Figure 20-29). In the discussions of mitosis, it is preferable or common to use the term chromosome to refer to the replicated structures that condense. During the prophase period of mitosis, the condensed chromosome is visible under the light microscope. Accordingly each chromosome is made of the two daughter DNA molecules following DNA replication and the histones as well as other chromosomal proteins that is associated with them (see Figure 10-27). The indistinguishable daughter DNA molecules and associated chromosomal proteins that is at this time seen as one chromosome are denoted as sister chromatids. Sister chromatids are associated to each other by protein cross-links lengthways. In vertebrates, sister chromatids become restricted to a single region of connotation called the centromere while chromosome condensation occurs. Throughout interphase, the portion of the cell cycle sandwiched by the end of one M phase and the start of the next, the outer nuclear membrane becomes continuous with the endoplasmic reticulum (see Figure 5-19). With the onset of mitosis in prophase, the nuclear envelope withdraws into the endoplasmic reticulum in a greater number of cells from higher eukaryotes, and Golgi membranes breakdown down into vesicles. In this moment, the mitotic apparatus is prearranged into a central mitotic spindle and a pair of asters (Figure 20-31a; see also Figure 20-2c). The spindle is a mirror-imaged packet of microtubules together with its associated proteins assuming an overall shape of a football. An aster is a start-shaped of microtubules found at each pole of the spindle. At each half of the spindle is a single centrosome which organizes three different factions of microtubules whose negative ends point at the centrosome (Figure 20-31b). One set forms the aster; they radiate toward the cortex of the cell away from the centrosome to assist in the positioning of the mitotic apparatus in order to determine the division plane during cytokinesis. The two remaining sets of microtubules is made of the spindle. During metaphase, the kinetochore, gathers at each centromere to allow for kinetochores of sister chromatids to interact with microtubules that originate from opposite spindle poles (see Figure 20-31). Sister chromatids separation occurs at the Anaphase of mitosis. In the initial stages, they are pulled by motor proteins lengthwise the spindle microtubules to the opposite poles and further separated as mitotic spindle lengthens (see Figure 20-40). Mitotic spindle aggregation stops and chromosomes condensation ceases immediately chromosome division is completed during telophase. Membrane begins to forms around the aggregated chromosomes again as they decondense. Cytoplasmic division, popularly denoted as cytokinesis, results in the production of two identical daughter cells and Golgi complex formation begins in each daughter cell. Subsequent to cytokinesis, the cell cycle enters the G1 phase, to begin another turn of even next in the cycle. Breakdown of nuclear envelope does not occur in yeasts and other fungi, during mitosis. In Such organisms, the mitotic spindle occurs within the nuclear membrane, and pinches off, to form two nuclei during cytokinesis.Vertebrates as well as diploid yeasts, cells have diploid (2n) chromosomal number at the G1 phase of mitosis and one of each of these pair of chromosomes is inherited from each parent. Human cells that replicate rapidly develop through the entire cell cycle in about a day (24 hours): with mitosis spanning a duration of approximately 30 minutes; G1, with an approximate duration of 9 hours; the S phase, with an approximate duration of10 hours; and G2, occurring somewhere for a period of 4.5 hours. In rapidly growing yeast cell however, the entire cycle is completed in approximately 90 minutes.In organisms like humans, characterized by multiple cells, most differentiated cells “leave” the cell cycle and live for days or weeks, and in some cases such as nerve cells, exit from the cell cycle could be permanent and hence will never divide again. Such postmitotic exits generally occurs at the G1 phase of the cell cycle, as the cycle prepares to enter the G0 phase (see Figure 21-1). It should be appreciated that some cells in the G0 phase may return to the cell cycle and resume replicating; this reentry is planned, thereby providing control of cell propagation. Regulation through the cell cycleThe concentrations of the cyclins, the regulatory subunits of the heterodimeric protein kinases that check cell-cycle activities, increase and decrease with cells progression into the cell cycle. The control subunits of aforementioned kinases, better referred to as cyclin-dependent kinases (CDKs), have no activity until they get associated with a cyclin. Each CDK can interact with different cyclins, and the type of cyclin it interacts with determines which proteins get phosphorylated by a particular cyclin-CDK composite. Figure 21-2 When cells are activatedted to replicate, G1 cyclin-CDK complexes are the first to be expressed. These complexes prepare the cell for the synthesis phase of the cycle by activating transcription factors that stimulate genes transcription that codes for enzymes needed for DNA synthesis and the genes that codes for the synthesis phase cyclins and CDKs. The activity of S-phase cyclin-CDK complexes is at this time held in check by inhibitors. As the G1phase climaxes, the G1 cyclin-CDK complexes initiate S-phase inhibitors degradation through phosphorylation and by effect stimulate their polyubiquitination through a multi-protein SCF ubiquitin ligase. Further degradation of the polyubiquitinated proteasomes inhibitors of liberates active S-phase cyclin-CDK complexes.Once they are activated, the cyclin-CDK complexes of S-phase adds inorganic phosphoryl group to regulatory sites in the proteins that form pre-replication complexes of DNA. These pre-replication complexes are assembled on replication origins as the G1 progresses. The phosphorylation also checks reassembly of different pre-replication complexes. This also makes sure that each chromosome is replicated only once during as the cell passes through the cell cycle. This also ensures that there is proper maintenance of chromosome number in the daughter cells. Cyclin-CDK complexes of mitosis are manufactured during the Synthesis phase and G2 phase, however, they are not active because by this time, their inhibitory sites are phosphorylated. The inhibitory site phosphorylation is maintained until DNA synthesis is climaxed. Immediately DNA synthesis is completed, there is a dephosphorylation of the inhibitory sites to activate the mitotic cyclin-CDK complexes. As they are activated, they are capable of phosphorylating multiple proteins that promote chromosome condensation, nuclear envelope retraction, mitotic spindle apparatus assembly, and align the condensed chromosomes to the metaphase plate. “As mitosis begins, the anaphase-promoting complex, APC, a multisubunit ubiquitin ligase, polyubiquitinates key regulatory proteins marking them for proteasomal degradation”. One efficient substrate of the APC is securin, the protein that hinders sister chromatids cross-limking degradation. Polyubiquitination of securin by the APC is inhibited to allow for the kinetochores to assemble at the centromeres of all chromosomes have made successful attachement to spindle microtubules, to ensure chromosomal alignment at the metaphase plate. Complete alignment of all chromosomes marks the beginning of APC polyubiquitinates of securing. This process leads to proteasomal disruption and an onward degradation of the cross-linking proteins that connects sister chromatids (see Figure 21-2, step ). This order of events starts anaphase by freeing sister chromatids to afford segregation to opposite spindle poles.Getting to the end of anaphase, the APC directs polyubiquitination and subsequently result in proteasomal disruption of the mitotic cyclins. Polyubiquitination of the mitotic cyclins by APC isrepressed until the separating chromosomes have reached their ideal location in the dividing cell (see Figure 21-2, step). Degradation of the mitotic cyclins result in the inactivation of the protein kinase effect of the mitotic CDKs. The quencequent decrease in mitotic CDK activity allows for the inherent active protein phosphatases to liberate the phosphates that were used to phosphorylate the specific proteins by the mitotic cyclin CDK complexes. As a result, the currently segregated chromosomes decondense, and there is reformation of nuclear membrane around daughter-cell nuclei. This also trigger the assembly of Golgi apparatus during telophase; lastly, the cytoplasm divides by a process called cytokinesis to yield the two daughter cells.Going into the G1 phase of the next cell cycle, there is dephosphorylation of pre- replication complexes proteins by phosphatases. These proteins were phosphorylated by S-phase cyclin-CDK complexes coming into the previous Synthesis-phase, and their phosphorylation had been sustained throughout mitosis by mitotic cyclin-CDK complexes. The dephosphorylation of these proteins in G1 makes it possible for new pre-replication complexes to be reassembled at replication origins in preparation for the next S-phase (see Figure 21-2, step ). Cdh1 Phosphorylation by G1 cyclin-CDK complexes in G1 deactivates it, and this allows accumulation of S-phase and mitotic cyclins in the succeeding cycle.How cell division influences the cell cycleThe process of cell cycle occurs through three critical transitions; G1 ? S phase, metaphase ? anaphase, and anaphase ? telophase and cytokinesis, is irrevocable owing to the fact that these transitions are initiated strictly regulated degradation of proteins, which in itself is an irreversible process. In view of that, there is an obligatory unidirectional passage of cells through the cell cycle. In complex organisms, the cell cycle control is achieved principally by controling the synthesis and effects of G1 cyclin-CDK complexes. Extracellular growth factors only act as mitogens by initiating synthesis of G1 cyclin-CDK complexes. The activity of these and other cyclin-CDK complexes is regulated by phosphorylation of specific inhibitory and activating sites in the catalytic proteins. As far as mitogens do act for a satisfactory duration, the cell cycle will continues to completion these protein complexes are removed. Restriction point is the period in late G1 where processes in the cell cycle becomes independent of mitogens (see Figure 21-2).Programmed cell death and apoptosisEvolution of multicellular organisms arose new mechanisms that diversified cell types, in order to direct cell production, size and number regulation, organize them into functional tissues, and to get rid of unnecessary or warn out cells. Communication between and among cells became even paramount than as it were in prokaryotic organisms. Another important phenomenon that evolved with evolution of eukaryotic organisms was the change in the mode of reproduction. Some cells became specialized as germ cells, eggs and sperm, and have the ability to give rise to new organisms upon stimulation. These specialized cells are distinct from all other body cells, known as somatic cells. The working conditions of these specialized cells when stimulated leads to the formation of working tissues and organs during development of multicellular organisms and depends in part on precise patterns of mitotic cell division. Programmed cell death is a term used to denote a cell’s fate, the fate, though abnormal, is critical to eukaryotic organisms. In fact, this phenomenon is responsible for keeping our hands from being webbed and our embryonic tails from persevering. Cellular communications control cell death in two essentially different ways. First, almost all cells in multicellular organisms need signals to stay alive. In in cases where these signals are not received cells affected activate a “suicide” suite. Secondly, definite signals induce a “murder” program that kills cells. It is noteworthy that in either of these circumstances, cell death is arbitrated by a common molecular pathwayProgrammed cell death occurs through apoptosisThe expiration of cells through programmed cell death is coordinated by a well-defined order of morphological changes, jointly called, apoptosis. Cells in admitted inthis program shrink and condense emancipating small membranebound apoptotic bodies, which are largely engulfed by other cells (Figure 22-26; see also Figure 1-19). The nuclei condense and the DNA is fragmented without releasing intracellular content into the extracellular milieu. The program is strict and critical at both embryonic and adult life to ensure maintenance of normal cell size, number and composition. Cell cycle and apoptosis meet Cell propagation and death regulation is obligatory in multicellular organisms in order to maintain tissue homeostasis. Several research findings indicates that the regulation could be accomplished, in part, by connecting the cell cycle process development and programmed cell death via the use and control of a shared set of factors. Findings that the link between the cell cycle and apoptosis originate from the accrued proof that when the cell cycle is altered, it could either thwart or trigger programmed cell death. An appreciable fraction of these facts has been determined with regards to tumor suppressor genes as those of p53 and RB, the dominant oncogene, c-Myc, and various CDKs and associated regulators. The fucntions of these proteins in cell cycle has been established in this text under the sub-heading, ‘regulation through the cell cycle’ and so it only needs be established that they also act to sensitize cells to apoptosis. Indeed, failure in the activities of either of these proteins can result in pathologic conditions such as neoplasias especially if the resulting effect is not answered by the appropriate cell death programing. In fact, there is no iota o doubt that converting knowledge extended by studying the relationship between cell death and cell proliferation could be the bridge that will aid in the quest for novel therapies to sidestep disease progression or improve clinical outcome.In both apoptosis and cell cycle processes, there is loss of substrate attachment, cell become become rounded, shrink, condense their chromatin and exhibit membrane blebbing. Notwithstanding the similarities in apoptosis mitosis, they share crutial differences. For illustration apoptotic cells’ DNA is degraded at internucleosomal linker sites, yielding DNA fragments in several 180 bp that consequently results in a nucleosomal ladder. Further to this, cell membrane proteins are cross-linked in apoptotic cells to enhance membrane rigidity 2, and apoptotic cells are characteristically engulfed by adjacent macrophages. In contrast however, there is DNA is segregation and the cell is divided by cytokinesis in mitotic cells to yield two healthy, daughter cells.More insights to support the argument courtesy of a relation between the cell cycle and apoptosis is founded in some instances where the genetic regulation of cell cycle progression is also involved in apoptosis. There is accumulating evidence that manipulation of the cell cycle may prevent or induce an apoptotic response depending upon the cellular context 5. The fact that cellular context is key, enough to prove that these proteins are more likely to tie programmed cell death to proliferative indicators even though they are not associated to the cell’s apoptotic machinery. It is most likely that these proliferative proteins are responsible for sensitizing cells before they are initiated into apoptosis especially p53 Myc, CDKs and pRb.p53 is a nuclear DNA-binding phosphoprotein that occurs typically as a tetramer able to bind specific DNA sequences. Activation of p53 occurs by increasing the protein’s half-life. Activation also increases the rate initiation its mRNA translation 18. 19.p53 impacts cell division by acting predominately in the G1 phase of the cell cycle progression. Oncogenic and hyperproliferative stimuli such as Myc, DNA damage by UV, and ?-irradiation, are the stimulus that trigger p53 activity 17. Once activated, p53 causes a G1 arrest by expressiing p21 gene which inhibits of CDKs. In such cases, phosphorylation of pRb does not occur and so cells are unable to progress through the G1-to-S-phase transition. Schneider and his colleagues have 20 reported p53 ability to control CAK activity leading down-regulation of CDK2. There is therefore an implication that p53 is directly involved in triggering growth arrest as it interacts with the CAK complex and so CDK inhibitors involvement would not berequired.Even though the mechanism behind the influence of p53 on G2/M growth arrest has ot been elucidated yet, several findings point out that p53 functions at the G2/M checkpoint 19. It must also be mentioned that the ability of p53 to induce a G2 arrest is cell-type-specific. Fairly repeatedly in several rats, humans and human cell lines excess expression of p53 have been proven to inhibit entry into mitosis 21. The condition for activation of this checkpoint however is when DNA synthesis is blocked and damaged or incompletely synthesized DNA segregation is prevented.There are also evidence of p53’s involvement in the spindle checkpoint to block re-replication of DNA in times that mitotic spindle is damaged, through inhibition of S-phase entry 24. Further to these, p53 is also involved in controlling centrosome duplication. In fact, it has been observed that p53 directly associates with centrosomes 25 and prevents mitotic failure regulating the number of centrosomes 26.The take home information here is that, evidence available indicates that the role of p53 in programmed cell death is chiefly experienced when cell cycle progression fails. This means that there is a permissive stimulus from cell division at not one and two but three phases of the cell cycle progression.