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Cell cycle and signaling

  1. Cell Cycle and Signaling
  2. › Introduction › Phases of cell division › Checkpoints › Meiosis › Mitosis › Checkpoints and cell cycle regulation › Significance of cell cycle Contents
  3. The cellular life cycle also called the cell cycle it includes many processes necessary for successful self-replication. Beyond carrying out the tasks of routine metabolism, the cell must duplicate its components most importantly, its genome so that it can physically split into two complete daughter cells. The cell must also pass through a series of checkpoints that ensure conditions are favorable for division. Cell Cycle
  4. The cell cycle consists of four distinct phases: G1 (Gap1) phase S phase (synthesis G2 (Gap2) phase (collectively known as interphase) and M phase (mitosis). M (mitosis) phase is itself composed of two tightly coupled processes: mitosis in which the cell's chromosomes are divided between the two daughter cells, and cytokinesis… in which the cell's cytoplasm divides in half forming distinct cells. Activation of each phase is dependent on the proper progression and completion of the previous one. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase… Phases of cell division
  5. G0 phase The G0 phase is a period in the cell cycle in which cells exist in a quiescent state. G0 phase is viewed as either an extended G1 phase, where the cell is neither dividing nor preparing to divide, or a distinct quiescent stage that occurs outside of the cell cycle. G0 is sometimes referred to as a "post-mitotic" state… G1 phase The first phase of interphase is G1 phase, from the end of the previous Mitosis phase until the beginning of DNA replication is called G1 (G indicating gap). It is also called the growth phase. During this phase the biosynthetic activities of the cell, which had been considerably slowed down during M phase, resume at a high rate. This phase is marked by synthesis of various enzymes that are required in S phase, mainly those needed for DNA replication…
  6. S phase Initiation of DNA replication is indication of S phase; when it is complete, all of the chromosomes have been replicated, at this time each chromosome has two (sister) chromatids. Thus, during this phase, the amount of DNA in the cell has effectively doubled, though the ploidy of the cell remains the same. Rates of RNA transcription and protein synthesis are very low during this phase. An exception to this is production of histone protein, which mostly occurs during the S phase.
  7. G2 phase After S phase or replication cell then enters the G2 phase, which lasts until the cell enters mitosis. Again, significant biosynthesis occurs during this phase, mainly involving the production of microtubules, which are required during the process of mitosis. Inhibition of protein synthesis during G2 phase prevents the cell from undergoing mitosis.
  8. In order to move from one phase of its life cycle to the next, a cell must pass through numerous checkpoints. At each checkpoint, specialized proteins determine whether the necessary conditions exist. If so, the cell is free to enter the next phase.. Each part of the cell cycle features its own unique checkpoints. For example, during G1, the cell passes through a critical checkpoint that ensures environmental conditions are favorable for replication. If conditions are not favorable, the cell may enter a resting state known as G0. Some cells remain in G0 for the entire lifetime of the organism in which they reside. For instance, the neurons and skeletal muscle cells of mammals are typically in G0. Checkout points
  9. › Another important checkpoint takes place later in the cell cycle, just before a cell moves from G2 to mitosis. Here, a number of proteins scrutinize the cell's DNA, making sure it is structurally intact and properly replicated. The cell may pause at this point to allow time for DNA repair, if necessary. › Yet another critical cell cycle checkpoint takes place mid- mitosis. This check determines whether the chromosomes in the cell have properly attached to the spindle, or the network of microtubules that will separate them during cell division. This step decreases the possibility that the resulting daughter cells will have unbalanced numbers of chromosomes a condition called aneuploidy
  10. › Process of cell cycle must be highly regulated so that each daughter cell contains the complement of DNA found in parent cell. › There are different mechanisms to control the timing of events in the context of different cell types. › Most important discoveries about mechanisms that control events of cell were elucidated using yeast › Results have shown many important control genes are present Checkpoints and Cell Cycle Regulation
  11. › Many cell cycle control genes in mammalian cells are also called cell division cycle genes. › Much of the control of the progression through the phases of a cell cycle are exerted at check points. CDC Genes Two most critical genes that occur near the end of G1 prior to S- phase entry and those near the end of G2 prior to mitosis
  12. › Heart of timing control is the responsibility of a family of protein kinases that are called CDKs › Oscillating changes in the activity of CDKs leads to oscillating changes in phosphorylation of various intracellular proteins. After phosphorylation the cyclins CDK complex is fully active. › Which then effect changes in events of cell cycle. Cyclin Dependent Kinase
  13. › The cyclical activity of each CDK is controlled by a series of proteins, the most important of which are cyclins. › CDK are dependent upon their interaction with the cyclins for activity unless they are tightly bound CDKs without kinase activity, level of various CDKs remain fairly constant throughout the cell cycle, their activities changes in concert with the fluctuations of cyclins Cyclins
  14. Four different types of Cyclins are there
  15. G1-Cyclins They are not found in all eukaryotes but those where they are synthesized they promote passage through a restriction point in late G1 called Start. G1/S-Cyclins They bind to their cognate CDKs at the end of G1 and it is the interaction that is required to commit the cell to the process of DNA replication in S-Phase S-Cyclins They bind to their CDKs during S-phase and it is the interaction that is required for the initiation of DNA synthesis. M-Cyclins They bind to their cognate CDKs and in so doing promote the events of mitosis.
  16. › CDKs are inactive unless bound to a cyclin, there is more to activation process than just the interaction of two parts of complex. › When cyclins bind to CDKs they alter the conformation of CDK resulting in exposure of a domain that is site for phosphorylation by another kinase called CDK activating Kinase. › Proteins that bind to and inhibit cyclin-CDK complexes are called CDK inhibitory proteins › CKI-cyclin kinase inhibitor (Example P21) Interaction of CDKs
  17. › The cyclical degradation of cyclins is affected through the action of several different ubiquitin ligase complexes they are two important ubiquitin ligase complexes. › One of them which function to control transit from G1 to S- phase and the other is called anaphase promoting complex. Ubiquitin ligase complexes
  18. › Controls the level of M-phase cyclins as well other regulators of mitosis. › Controls initiation of sister chromatids separation which begins at metaphase-anaphase transition. Anaphase promoting Complex
  19. › Mitosis is a process where a single cell divides into two identical daughter cells (cell division). › During mitosis one cell? divides once to form two identical cells. › The major purpose of mitosis is for growth and to replace worn out cells. › If not corrected in time, mistakes made during mitosis can result in changes in the DNA? that can potentially lead to genetic disorders?.
  21. Interphase › The DNA in the cell is copied in preparation for cell division, this results in two identical full sets of chromosomes?. › Outside of the nucleus? are two centrosomes, each containing a pair of centrioles, these structures are critical for the process of cell division. › During interphase, microtubules extend from these centrosomes.
  22. › In this stage the nuclear envelope breaks down . › Some mitotic spindle fibers elongate from the centrosomes and attach to kinetochores. › Other spindle fibers elongate but instead of attaching to chromosomes, overlap each other at the cell center. - Prometaphase
  23. › The chromosomes line up neatly end-to-end along the centre (equator) of the cell. › The centrioles are now at opposite poles of the cell with the mitotic spindle fibres extending from them. › The mitotic spindle fibres attach to each of the sister chromatids Metaphase
  24. › The sister chromatids are then pulled apart by the mitotic spindle which pulls one chromatid to one pole and the other chromatid to the opposite pole. Anaphase
  25. › At each pole of the cell a full set of chromosomes gather together. › A membrane forms around each set of chromosomes to create two new nuclei. › The single cell then pinches in the middle to form two separate daughter cells each containing a full set of chromosomes within a nucleus. This process is known as cytokinesis Telophase & cytokinesis
  26. › Meiosis is the form of eukaryotic cell division that produces haploid sex cells or gametes (which contain a single copy of each chromosome) from diploid cells (which contain two copies of each chromosome). › The process takes the form of one DNA replication followed by two successive nuclear and cellular divisions (Meiosis I and Meiosis II). Meiosis
  27. › Two successive nuclear divisions occur › Meiosis I (Reduction) › Meiosis II (Division). › Meiosis produces 4 haploid cells. › Mitosis produces 2 diploid cells. Phases of Meiosis
  28. › Prophase I has a unique event -- the pairing of homologous chromosomes. › Synapsis is the process of linking of the replicated homologous chromosomes. › The resulting chromosome is termed a tetrad, being composed of two chromatids from each chromosome, forming a thick (4-strand) structure. › Crossing over may occur at this point. › During crossing-over chromatids break and may be reattached to a different homologous chromosome. › crossing-over between homologous chromosomes produces chromosomes with new associations of genes and alleles. Prophase 1
  29. Metaphase I › Metaphase I is when tetrads line-up along the equator of the spindle. Spindle fibers attach to the centromere region of each homologous chromosome pair. Other metaphase events as in mitosis
  30. › Anaphase I is when the tetrads separate, and are drawn to opposite poles by the spindle fibers. The centromeres in Anaphase I remain intact. Anaphase I
  31. › Telophase I is similar to Telophase of mitosis, except that only one set of (replicated) chromosomes is in each "cell". Depending on species, new nuclear envelopes may or may not form. Some animal cells may have division of the centrioles during this phase. Telophase I
  32. › During Prophase II, nuclear envelopes (if they formed during Telophase I) dissolve, and spindle fibers reform. All else is as in Prophase of mitosis. Indeed Meiosis II is very similar to mitosis Prophase II
  33. › Metaphase II is similar to mitosis, with spindles moving chromosomes into equatorial area and attaching to the opposite sides of the centromeres in the kinetochore region Metaphase II
  34. › During Anaphase II, the centromeres split and the former chromatids (now chromosomes) are segregated into opposite sides of the cell. Anaphase II
  35. › Telophase II is identical to Telophase of mitosis. Cytokinesis separates the cells. Telophase II
  36. › The hereditary material is equally distributed in the daughter cells and the genetic information remains unchanged generation after generation. › Mitosis results in an increase in size and growth of an organism. › Mitosis gives rise to many cells which differentiate to form tissues and organs of the organism › Regeneration, healing of wounds and replacement of older cells all are the gifts of mitosis › Organism requires, managed, controlled, and properly organized process of mitosis if not so it will result in malfunction, unwanted tumors and lethal diseases like cancers. Significance of mitosis
  37. › Crossing over and random assortment of chromosomes are two significant happenings of meiosis. › During crossing over, parental chromosomes exchange segments with each other which results in a large number of recombination’s › Meiosis allows for new combination of genes to occur in the gametes(cells involved in sexual reproduction). › Meiosis increases genetic diversity, continue evolution, and maintain a species. Significance of meiosis
  38. › Deletion: Sometimes during mitosis the chromosomes can be damaged. If the chromosome gets broken the fragments can be lost. If this happens the genetic material they contain is deleted. › Translocation: If the chromosome breaks, it can reattach to another chromosome. Sometimes it reattaches to the wrong chromosome. › Inversion: When the fragment gets reattached it gets attached to the right chromosome but upside down. When this happen it incorrectes codes for information. › Non-disjunction: Failure of paired chromosomes to separate (to disjoin) during cell division,one cell is given three copies (trisomy) of a chromosome while the other gets only one (monosomy). Nondisjunction causes errors in chromosome number. Errors
  39. › Patau syndrome › Down syndrome › Cri-du-chat syndrome › Turner syndrome › Klinefelter syndrome Consequences
  40. › Patau's syndrome have an extra copy of chromosome 13 in every cell of their body. it is also called trisomy 13. It is the most severe of all chromosomal abnormalities which result in severe physical and mental impairment as well as developmental delay. Patau's syndrome
  41. › Down syndrome is a genetic condition. It occurs when a child is born with 47 chromosomes instead of the usual 46. The extra chromosome causes delay in brain development and physical abnormalities. There symptoms are:  loose muscles and joints  a small mouth and small head shape that is flatter at the back  lower than average birth weight short  Small ears Down syndrome
  42. › The name of this syndrome is French for "cry of the cat," referring to the cry of children with this disorder. Cri-du-chat is caused by a deletion on the short arm of chromosome 5. › A deletion is caused by a break in the DNA molecule that makes up a chromosome. › People who have cri-du-chat have a small head an unusually round face, a small chin, widely set eyes and folds of skin over their eyes. Cri-du-chat syndrome
  43. › Turner syndrome (TS) is a medical disorder that affects about 1 in every 2,500 females. Most females are born with two X chromosomes, but females with Turner syndrome are born with only one X chromosome. These females are sterile. Turner syndrome
  44. › Mitosis is closely controlled by the genes inside every cell. › Cancer is essentially a disease of mitosis - the normal 'checkpoints' regulating mitosis are ignored by the cancer cell. Cancer starts with one normal cell changing into a cancerous cell;this may be due to a mutation in the cell's DNA that affects its growth. › Mass of cancer cells is called a tumor. When a tumor spreads to another part of the body it is said to be metastasized. Cancer (uncontrolled cell division)