Cells & Genes Essay - Eukaryotic cell cycle PDF

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Cells & Genes
Eukaryotic cell cycle tutorial essay...

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Describe the eukaryotic cell cycle, discuss how it operates and is coordinated with cell growth, and give examples of how its progression is regulated.

The Eukaryotic Cell Cycle by Kylie Dong Each cell undergoes a cell cycle in which is is created, grows, and then dies to make room for new cells. The most basic function of the cell cycle is to copy the DNA in the cell, allow the cell to grow, and then duplicate the cell into two identical daughter cells. The large number and variety of proteins and hormones must regulate the stages of the cycle very carefully in order to prevent errors (Alberts et al, 2002). Various signals also control the growth of cells themselves in size and the number of cells in a particular tissue for example an embryo divides rapidly at first, increasing it’s number of cells in order to increase in size. This is stimulated by particular proteins that allow it to bypass the growth phases of the cell cycle so it can increase in cell number quicker (Cooper, 2000). Overview of cell cycle The cell cycle consists of many stages. The two main stages are interphase and mitosis. Within interphase there are two growth phases, G1 and G2, with the S-phase/DNA synthesis or replication occurring in between in preparation for mitosis. Mitosis consists of 4 distinct stages: prophase, metaphase, anaphase, telophase. This is followed closely by cytokinesis by which the cells divides into two new cells and the cell cycle begins again in each new cell. In a standard human body cell rapidly dividing with a total cycle time of 24 hours, the G1 phase would last 11 hours, the S phase 8 hours, G2 phase 4 hours, and M phase 1 hour. The lengths of each stage can be proven by an experiment in which cells are exposed to radioactive thymidine then culture for varying lengths of time. Radioactively labelled interphase cells will be observed for several hours as they progress through the S-stage into the G2 stage. By comparison, radioactively labelled mitotic cells will not be observed until 4 hours after labelling which corresponds (Cliff, 2016) to the length of the G2 stage, the minimum time required for a cell to incorporate the radioactive thymidine at the end of S phase to enter mitosis (Cooper, 2000). Mitosis Mitosis is a large part of the cell cycle and is the process by which the DNA, organelles, and cell itself divides into two new identical daughter cells. Mitosis begins with prophase when the chromosomes are already replicated and each consists of two sister chromatids held together by a centromere. These chromosomes condense in the nucleus. Outside the nucleus, the

mitotic spindle forms between two centromeres which have replicated and moved apart. Next prometaphase occurs as the nuclear envelope is broken down and spindle microtubules attach to the chromosomes. Then at metaphase the chromosomes are aligned on the equator of the cell by the spindle microtubules. Crossing over of the chromosomes occurs at this step. As does independent assortment of the chromosomes during meiosis. Next at anaphase the sister chromatids in each chromosome are pulled to opposite sides of the cell by the spindle microtubules as they shorten and the spindle poles move apart. The during telophase the two sets of daughter chromosomes arrive at the poles of the spindle and decondense. A new nuclear envelope forms around each set creating two nuclei in the cell and marking the end of mitosis. Cytokinesis occurs after mitosis and divides the cell down the middle into two new daughter cells by the contraction of a contractile ring made of actin and myosin filaments (Alberts et al, 2002). S-phase/DNA synthesis DNA synthesis is a key step to the cell cycle and cell duplication because the DNA contains the crucial information a cell needs to survive. DNA replication must occur with speed and accuracy and it is also crucial it occurs only exactly once per cell cycle at the exact time it is needed. The beginning of the cell cycle or the “Start” point is also the beginning of the S-phase or DNA synthesis. It begins firstly by the unwinding of the DNA double helix by DNA helicase and DNA synthases are loaded onto the two single DNA strands. Elongation then occurs where new nucleotides are added to the old DNA template strands by DNA synthase to create new DNA. To ensure DNA synthesis only occurs once per cycle, the initiation phase is divided into two steps that occur at different times. The first step occurs in late mitosis and the early stages of growth phase one when a pair of inactive DNA helicases are put on the replication origin point forming a rereplicative complex. The second step occurs in the S-phase. Once the DNA has started replicating from the origin site, the origin cannot be reused until a new prereplicative complex is assembled there and this only occurs once per cycle (Alberts et al, 2002). Growth phases 1 and 2 During the growth phases the cells themselves increase in size. This is also when organelles like mitochondria can divide by a replication similar to binary fission. Growth factors stimulate this increase in cell mass by promoting the synthesis of proteins and other macromolecules in the cell and inhibiting their degradation. In G1 the cell makes a variety of proteins needed for DNA synthesis in preparation. In G2 the cell also makes a variety of proteins needed for the cell cycle and its regulations. It also makes the microtubules needed for mitosis in preparation for the next stage of the cell cycle (Fricker, 2016). Cell cycle regulation The cell cycle control system acts like a timer that triggers events in a set sequence. Delays can be programmed to occur if errors occur, for example if a malfunction occurs in DNA synthesis, the cell can be signalled to delay progression to the M phase so incorrectly replicated chromosomes aren’t used in the rest of the cycle. The cell cycle’s control systems are a series of biochemical switches that are generally binary and irreversible. This assures steps such as chromosome condensation are done to completion. Back up systems make the cell cycle

control system more robust and reliable so that even if errors occur, other systems allow operation. The system is also highly adaptable and can be modified to suit different cell types or respond to intracellular and intercellular signals. The cell cycle control system governs progression at 3 major points of the cycle. The first is “Start” in the late parts of the first growth phase as the cell enters into DNA duplication. The second is at the end of the second growth phase and start of mitosis. The third is the metaphase to anaphase transition at the end of mitosis and beginning of cytokinesis when the system stimulates the separation of the sister chromatids. If conditions are entirely unfavourable for cell replication, the system pauses the cell cycle at “Start” until conditions become favourable again (Alberts et al, 2002). Regulation by cyclically activated cyclin dependent protein kinases and cyclins Cyclically activated cyclin dependent protein kinases (Cdks) are central components which control the cell cycle system. The activity of these kinases rise and fall in the cell as the cycle progresses leading to changes on phosphorylation of intracellular proteins which initiate or regulate major events. For example an increase in cdk activity between the second growth phase and mitosis induces the phosphorylation of proteins that control chromosome condensation, nuclear envelope breakdown, spindle assembly, and other early mitosis events. Cyclical changes in Cdk activity are controlled by a complex array of enzymes and proteins but the most important of these are cyclins. Unless Cdks are bound to a cyclin, they have no protein kinase activity. Cyclins undergo a cycle of synthesis and degradation each cell cycle whereas the levels of Cdks are constant. It is the assembly of the cyclin-cdk complexes when cyclins are present that cause events at specific stages of the cell cycle. There are 4 classes of cyclins, each of which are defined by the stage of the cell cycle at which they function by binding to Cdks. G1/S-cyclins activate Cdks in the late stages of the first growth phase to help trigger the “Start” then their levels fall in S phase. S-cyclins bind to Cdks soon after “Start” and help stimulate late chromosome replication. Their levels stay up until mitosis and they contribute to the control of some early mitotic events. M-cyclins activate Cdks at the end of growth phase two, going into mitosis to stimulate mitosis and their levels fall mid mitosis. Then the G1-cyclins help govern the activation of the G1/S-cyclins. In yeast cells there is one type of Cdk that binds to all the classes of cyclins but in vertebrate cells there are four Cdks. Two interact with G1cyclins, one with G1/S and S-cyclins, and one with S and M-cyclins (Alberts et al, 2002). The cyclin-cdk complex triggers different cell events by directing the Cdk to specific target proteins and phosphorylating these substrate proteins. Cdk activity can also be suppressed by inhibitory phosphorylation and inhibitor proteins in order to regulate the cell cycle by a method other than the rise and fall of cyclin levels (Alberts et al, 2002). Another method by which cyclin-cdk complex activities are regulated is by the destruction of proteins. This occurs in the metaphase to anaphase transition by anaphase promoting complex or cyclosome (APC/C) that is a ubiquitin ligase enzyme. These enzymes destroy proteins, one example is securin which protects the protein links that hold sister chromatids together in metaphase and its destruction brings about anaphase. APC/C also breaks down S and M-cyclins which inactivates most Cdks in the cell and this is crucial for the end of mitosis and cytokinesis. Then in late growth phase one, APC/C is turned off to allow accumulation of the cyclins once again. SCF is another ubiquitin ligase enzyme and this functions in late growth phase one to control the activation of S-Cdks and DNA replication. It also destroys G1/S-cyclins in the early S phase.

APC/C and SCF are both large multisubunit complexes. APC/C is regulated by changes in its subunits whereas SCF is regulated by phosphorylation of if its target proteins. Changes in cyclin gene expression can also control cyclin levels in cells and therefore regulates the cell cycle. In the discovery of cyclin-cdk complexes, maturation or mitosis promoting factor (MPF) was one of the earliest to be found. MPF was discovered in 1971 by Masui and Markert in an experiment done with frog oocytes (Masui and Markert, 1971) It consists of two subunits of cyclin dependent kinase (cdk) and cyclin B. MPF promotes the entrance into mitosis from the second growth phase by phosphorylating multiple proteins needed for mitosis. MPF is activated at the end of G2 by a phosphatase, which removes an inhibitory phosphate group added earlier. The MPF is also called the M phase kinase because of its ability to phosphorylate target proteins at a specific point in the cell cycle and thus control their ability to function (Fricker, 2016). In conclusion, the eukaryotic cell cycle operates in a particular way in which each step is very carefully regulated by proteins so that cells can grow and divide as efficiently and accurately as possible. Most cells follow a similar cell cycle pattern but eukaryotic cells have particular proteins in common that govern these processes showing a preservation of these traits from an ancient ancestor. These particular proteins must have been advantageous enough to be maintained and so are nearly always consistently present in eukaryotic cells, carrying out the same functions. They are a prime example of the complex yet very proficient systems created for us by the trials and errors of evolution. Sources: 2016. Eukaryotic Cell Division: The Cell Cycle. Cliff Notes. Retrieved 8 Mar 2016 from http://www.cliffsnotes.com/study-guides/biology/plant-biology/cell-division/eukaryote-celldivison-the-cell-cycle Dr Mark Fricker, 24 Feb 2016, Oxford University Department of Zoology Lecture: ‘Regulation of the cell cycle’ Y. Masui, C.L Markert. 1971. Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. Journal of Experimental Zoology. 177: 129-145 B. Alberts, A. Johnson, J. Lewis, M. Raff, K. Roberts, P. Walter, 2002, Molecular Biology of the Cell fourth edition. Garland Science G.M. Cooper, 2000, The Cell: A Molecular Approach. 2nd ed. Sinauer Associates...