Cell divisions and the cell cycle.docx

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Biomedical Sciences
Prof.Christina Mitchell

Cell divisions and the cell cycle. Discuss the basic principles of cell growth and cell division Cells reproduce by duplicating their contents and then dividing into two new cells. While the details of cellular replication can vary among different organisms, certain characteristics are universal. The DNA must be faithfully replicated, The replicated chromosomes must be segregated into two daughter cells and the majority of cells, double their mass and duplicate all their cytoplasmic organelles in each cycle. This follows the general strategy of; cell growth and chromosome replication, chromosome segregation and finally cell division. Chromosomes are made up of DNA, complexes with proteins in highly organised structures. The length of a single DNA molecule in the average human chromosome is ~3cm. There are Discuss the stages of the eukaryotic cell cycle The major events of the cell cycle are chromosome duplication, Mitosis and eventually cytokinesis. The cell cycle consists of four distinct stages, G1 phase, S phase (synthesis), G2 phase (collectively known as interphase) and M phase (mitosis). The M phase itself is composed of two tightly coupled processes. One is mitosis, the process in which the duplicated chromosomes are divided between the two sister cells. And cytokinesis, this is the process by which the cells cytoplasm divides in half, giving rise to two distinct cells. Activation of each phase is dependent on the proper progression and completion of the previous phase. Go phase is termed the ‘post-mitotic phase’ or resting phase. It is a period in the cell cycle when the cells exist in a quiescent state. Cells in this state are not dividing nor preparing to divide. Cells remain in this phase until they are induced by factors to divide. In this time cells carry out their function. Interphase is a period in the cell, where it prepares itself for division. It is therefore also known as the preparatory phase, no nuclear or cytosol division occurs, instead the cell take in nutrients to prepare for division. It proceeds in 3 stages, G1, S and G2. G1 phase is the first phase of interphase, it is marked from the end of the previous M phase until the beginning of DNA synthesis. Also termed the growth phase, biosynthetic activates of the cell, resume at a high rate. It is in this stage the proteins and enzymes required for s phase are made, particular those required for DNA replication. This phase is modulated by the p53 gene. S phase is marked by the commencement of DNA replication and is complete when all of the chromosomes have been replicated. G2 phase is simple the gap between DNA replication and mitosis. The cell continues to grow though this stage uses a checkpoint control mechanism to ensure that the cell is ready to undergo mitosis. Describe some details of cell division, focusing on mitosis. Mitosis, or M phase, involves nuclear division and is broken down into several distinct and sequential stages known as prophase, metaphase, anaphase, telophase and ultimately cytokinesis. Though minor variations exist, the processes that occur in M phase to divide on cell into two follow the same sequence in all eukaryotes. It involves the cells assembling, utilising and then dismantling the machinery required to pull the duplicated DNA apart and spilt the cytoplasm into two separate cells. The mitotic spindle and contractile ring are important mechanisms for this process and are unique to the M phase. The first readily visible manifestation of an impending M phase is a progressive compaction of chromatin into threadlike chromosomes. This is termed chromosome condensation and is required for the subsequent organised segregation of the chromosomes into daughter cells. Since histone H1 is present at a concentration of about one molecule per nucleosome and is known to be involved in the packing of nucleosomes together, its phosphorylation by mitotic phase promoting factor (MPF) at the onset of the M phase is thought to contribute to chromosome condensation. The Cytoskeleton in m phase changes thought the phase to accommodate and initiate division. The mitotic spindle assembles first and segregates the chromosomes. The contractile rings assembles later and divides the cell in two. The formation of each structure depends on different sets of proteins, this formation occur independently though is usually coordinated. The centrosome is the principle organising centre for cell division in most animal cells. It is a cloud of poorly defined pericentriolar material (centrosome matrix) associated with a pair of centrioles. During interphase the centrosome matrix nucleates cytoplasmic array of microtubules, which project outward toward the cell perimeter and their minus ends attach to the centrosome. Before a eukaryotic cell divides, it must duplicate its centrosome to provide one for each of its two daughter cells. The duplicated chromosomes are required to create the two daughter cells as the centrosomes form the two poles of the mitotic spindle. Prophase involves the chromatin condensing into discrete chromosomes. This occurs within an intact nuclear envelope. In the cytosol centrosomes begin to migrate to opposite ends of the cell and mitotic spindles form. The sister chromatids are held in the centre by kinetochores. Prometaphase involves the movement of the centrosomes to the spindle poles and the disruption of the nuclear envelope enabling the microtubules to gain access to the chromosome kinetochores. Metaphase involves the alignment of the chromatids at the equator along the metaphase plate. Anaphase involves the separation of sister chromatids due the shortening of the kinetochore microtubules. Telophase involves the complete migration of chromosomes to the opposite sides of the cell, they begin to have a nuclear envelope develop around them Cytokinesis involves the division of the cytoplasm by the contractile ring. This is comprised of actin and myosin filaments, which act to pinch the cell in two. A complete nuclear envelope surrounds the chromosomes which being to decondense. This ends with a fully replicated copy of the original cell and marks the end of cellular division. Both cells are able to go through the process to duplicate themselves. Various checkpoint mechanisms exist to ensure that condition are favourable for proper cell cycle progression. Cell cycle regulations and the role of cyclins Discuss the control of progression of the cell cycle between successive mitosis events Cell-cycling is a tightly controlled event, it relies on the turning on and off of genes and the activation or inactivation of proteins. The starting and stopping of processes such as DNA replication and mitosis are easily observed, though there are many others that are not. These events must too undergo regulation, in order to keep normal function. the cell cycle control system is a cyclically operating biochemical device contricted from a det fo interacting proteins that induced and co-ordiate the essential downstream processes that duplicate the cells and divide the content. This control system is regulated by breaks that can stop the cycle at specific checkpoints. At such checkpoints, feedback signals conveying information about downstream processes of the control system itself so as to prevent the next down-stream process. It also allows the cell cycle control system to receive information about its environment. Such checkpoints include, the entry from the cell cycle to the s phase, is the environment favourable. If it should enter mitosis (g2/m phase), is the environment favourable and is all DNA replicated? Should the transition from metaphase to anaphase occur, are al chromosomes attached to the spindle. Discuss the role of cyclins and CDKs The cell cycle control system is based around two families of proteins. Cyclins-dependent kinases (CDK) and cyclins. CDKs induce downstream processes by phosphorylating proteins on serine/threonine residues. Cyclins are regulatory subunits that bind to CDK molecules and control their ability to phosphorylate appropriate target proteins. The binding of a cyclin however, is only one of the four distinct ‘inputs’ required to activate a CDK. It also requires the addition of a phosphate to a specific threonine side chain (2 input), a phosphate elsewhere in the protein must rd th be removed (3 input) and the association of specific inhibitory molecules (4 input). CDK remains inactive until the binding of cyclin initiates its priming for activation. Cyclin synthesis leads to accumulation, and rising levels result in binding to CDK, though this is not enough to activate the CDK. The complex forms, though phosphorylation on try blocks the active site. The phosphorylation of try on another site and removal of try results in activation of CDK. The activate CDK can phosphorylate phosphatase, which activates more CDK. CDK can also phosphorylate DBRP, which triggers addition of ubiquitin molecules to cyclin by ubiquitin ligase. The cyclin is degraded by a proteasome, leading to inactive CDK. In mammalian cells over a dozen cyclins have been identified. They have been found to synthesise and degrade in a precisely timed sequence within the cell. It is regulated at the level of transcription as well as targeted via the ubiquitin pathway. D and E cyclins are expressed during G0/G1 and are referred to as start cyclins. This is the point at which cells commit to another round of DNA replication. D type cyclins are expressed in response to growth factors or mitogens and rapidly degrade when mitogens are withdrawn. Mitogens bind to cell surface receptors t
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