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The cell jfzufzufzjgxjgxjgxjgxjjgxkkkgcjgxjgxjgxkgxkgxigxigxugxjgxkgxigzifzifxcycle 35.ppt
- 1. CELL CYCLE
- 3. KEY CONCEPT Cells have distinct phases of growth, reproduction, and normal functions.
- 4. Why should you care about cell division? •How does a one-celled embryo grow into a multi- cellular organism? • When do cells need to be made in adults? ex. skin cells in humans are continuously being sloughed off and replaced - as many as 100 billion (1011) cells are lost daily • In abnormal situations, cells may divide “out of control” = cancer
- 5. Why cells divide- •Growth •Development • Repair of the organism
- 6. Why You Need To Learn ? Strictly Regulatory process. Loss of regulation Autonomous proliferation of cells Neoplasm Benign cells Malignant cells Carcinoma Sarcoma Leukemia
- 8. Objectives At the end of the lecture student should be able to; Explain the significance of the cell cycle in eukaryotes Name the phases of cell cycle Briefly explain the major events in each phase Briefly explain how the cell cycle is regulated Briefly explain the programmed cell death and its biological significance
- 9. Phases of cell cycle M – Mitotic phase G – Growth phase
- 10. Cell cycle • The cell cycle is a set of biochemical events driven by a control system that tells cells whether they can enter the next phase of the cell cycle Under normal conditions cell number is under control by regulation of cell cycle modulation of programmed cell death (apoptosis)
- 11. If the cell is not respond to the control system. Cancer cells do not respond normally to the body's control mechanism. ◦ They divide excessively and invade other tissues ◦ If left unchecked, they can kill the organism Cancer cells do not exhibit contact inhibition ◦ If cultured, they continue to grow on top of each other when the total area of the petri dish has been covered
- 12. • During this time organelles are reproducing, protein synthesis is occurring for growth and differentiation. • Because, transcription is occurring, the DNA is uncoiled. • This phase is the most variable, ranging from almost nothing to years. The G1 Phase of the Cell Cycle
- 13. The G1 Phase of the Cell Cycle Grows in size •Cells begin synthesize all the cellular components (mitochondria, ribosomes) needed to generate daughter cells. •Increases its supply of proteins Cells arrested in G1 may no longer have the capability of reproducing and are said to be in G0. Most cells that differentiate will do so during this phase.
- 14. Cells that have temporarily or reversibly stopped dividing are said to have entered a state of quiescence called G0 phase.
- 15. Two types of cells in G0 phase • Reversible • Irreversible Reversible (quiescent) – • Mature hepatocytes • Stem cells – Muscle Neural, Intestinal
- 16. Irreversible(differentiated and senescent) These cells must live as long as the organism itself, Differentiated All well differentiated cells oMuscle, oCardiac oneuronal
- 17. Senescent Cellular senescence is a permanent state of cell cycle arrest • Stresses.( tissue remodeling, injury, cancer, and aging) • Aging - Senescence is responsible of aging-related disorders (osteoarthritis , and atherosclerosis progressive functional deterioration. ) • In embryogenesis & tissue remodeling-proper development of the embryo and tissue repair • In cancer, senescence works as a potent barrier to prevent tumorigenesis.
- 18. The S or synthesis phase is the second phase of the cell cycle. •DNA uncoils •DNA replication occurs •Additional organelle replication occurs •This phase ensures that each emerging daughter cell will have the same genetic content as the mother cell. S Phase of the Cell Cycle
- 19. The G2 or Gap 2 phase occupies the time from the end of S until the onset of mitosis. •During this time, the cell prepares for mitosis by making and organizing necessary proteins such as the tubulin needed to construct microtubules which used to make spindle fibers. •On the average this phase may take four hours. G2 Phase of the Cell Cycle
- 20. • During mitosis the nucleus is replicated and the cytoplasm divides to produce two genetically identical daughter cells. • Remember that the DNA is replicated in S prior to mitosis. • The phases are triggered by the accumulation of cell signals. M Phase or Mitosis
- 22. Regulation of the Cell Cycle Where? Main Check Points – G1 check point S check point G2 check point M check point
- 24. 24 • The control of the cell cycle is dependent on an accumulation of “signal molecules”. • These signal molecules must be phosphorylated in order to be functional. Regulation of the Cell Cycle
- 26. • Cyclins are a family of proteins that control the progression of cells through the cell cycle by activating cyclin-dependent kinase (Cdk) enzymes. • Only with the cyclin is the Cdk active. • Cyclins were originally named because their concentration varies in a cyclical fashion during the cell cycle. • A kinase is a type of enzyme that transfers phosphate groups from high-energy donor molecules, such as ATP, to specific substrates, a process referred to as phosphorylation. 26 Cyclins vs. Kinases
- 27. 27 Cyclins vs. Kinases • Certain cyclins are made at certain times during the cell cycle, and their concentration will rise and fall. Cyclins are also destroyed after they are no longer needed by the cell. • CDKs are not destroyed as they are only activated or deactivated. • Which cyclin affects which phase of the cycle?
- 28. • MPF - the maturation-promoting factor /mitosis-promoting factor/ M-Phase promoting factor. • 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. M-Phase promoting factor ( MPF)
- 29. An example of how MPF initiates mitosis …. MPF promotes the entrance into mitosis (the M phase) from the G2 phase by phosphorylating multiple proteins needed during mitosis. The steps follow: • The nuclear lamina depolymerizes causing it to disassemble which in turn causes the nuclear membrane to disassemble • Histone H1 binds to the DNA in chromosomes, causing the chromosomes to condense • Cytoskeletal proteins allow cytoskeletal filaments to assemble which leads to: – Formation of the mitotic spindle which separates the daughter chromosomes – formation of the cleavage furrow by microfilaments which allows cytokinesis (constricting the cell at the center) to occur resulting in the formation of two new cells
- 30. 30 Once the CDK phosphory-lates certain signals, the cyclin is destroyed. In the cell, the concentration of cyclins will rise and fall depending on the phase of the cell cycle. When the cyclin is destroyed the Cdk returns to an inactive form (it is NOT destroyed!).
- 32. Nobel Prize in Physiology and Medicine 2001 Paul Nurse
- 33. Summary Significance of the cell cycle in eukaryotes Phases of cell cycle Major events in each phase Regulation of the cell cycle
Editor's Notes
- Once the new cell produce by parent cell it starts growing and then it produce daughter DNA which is essential for the daughter cell and later it will be divided into cells. This is the process that occurs is known as cell cycle
- 2.so there are mainly three areas to discuss when you talk about the cell cycle. 1.the growth of the cell 2. Getting ready for the next cell to synthesize ( DNA replication) 3. The cell division is the division of the cells into daughter cells. 1st and 2nd will be learning today. 3rd will be during the next lecture
- 3.Why should we learn about this? As we are aware we all started with a single cell which is fertilized ovam , from a single cell we now have uncountable number of cells. During the growth of an individual, this single cell multiplies. Before the multiplication, cell has to grow and synthesise New DNA which are the required for the cell division. During this growth , there are certain things that we have to control, and sometimes certain cells we have to remove from the site, it is just not the division but there are a lot of regulations should occur.
- Cell divide during the growth and development and then repair if there is a damaged. This process is very tightly regulated specially to stop unwanted proliferation.
- Once the regulation is loosened there will be abnormal cell proliferation which can lead to neoplasm. Neoplasm is when there is an abnormal proliferation of certain tissue cells, they can be dangerous like malignant cells or can be benign cells. Malignant cells are very fast-growing harmful cells. They are called carcinoma and sarcoma. Sometimes when they happen in the blood cells, we call leukemia.
- There are a few pictures that I want to show you. These are abnormal proliferation in the skin those are called skin tags. This is a benign kind of tumor, and all these others are an abnormal proliferation of abnormal cells. These cause cancers. This is cancer in the mouth, and this is in the sarcoma, cancer in the muscle this child is having a blood cancer we call it leukemia.
- What are the objectives of the lecture, you should be able to explain the significance of a cell cycle. You should be able to name the phases of the cell cycle, then you should be able to briefly explain the major events on each phase. There are several phases that we are going to study you should be able to explain the major events that occur there. Then should be able to briefly explain how the cell cycle is regulated which is an important part of the body and finally should be able to briefly explain the programmed cells with their biological significance. There is a process that program the cells to remove from the cycle that is called apoptosis.
- When you look at the cell cycle, a set of biochemical events driven by a control system that tells the cells when they can enter into the next phase of the cycle. For conventional purposes, we have divided the cell cycle into several phases. We are learning the events that occur in each phase. We divided the cell cycle into two main phases, the inter-phase and division phase or M-phase. The interphase is about 23-24 hours whereas the m-phase S-phase, so you have learned about this S-phase in previous lecture on DNA replication. it requires about 12 hours and that is the longest period of the cell cycle, it’s about half of the cell cycle. And then the M phase is where the cell division occurs. It doesn’t take much time. It’s less than an hour in a mammalian cell. Typical human cell proliferating in culture, interphase might occupy 23hours of a 24 hour cycle, with 1 hour for M phase.
- This cycle regulates tightly so then if there is a problem cycle says you have to stop here and allow to correct and then if cell is alright, will be asked to move to the next phase. We’ll learn that in detail later,
- Some cells will be going into the G0 phase so they will no longer be inside the cell cycle they move to some sleeping position. Almost all cells in our body are differentiated cells that which are in G0 phase. Look at the G0 phase, they can be in the G0 phase temporary, or permanently. Depending on that we divide this G0 phase into two types. Reversible G0 and irreversible G0. The cells which are in the reversible G0 phase are, for example, hepatocytes, all the stem cells, (the pluripotent cells they become stem cellsand they are immature cells for other tissues). They are in a dormant stage, when necessary, they will come to the cell cycle and proliferate.. So, they are reversible. This shows some pictures of reversible cells. And there are some irreversible cells. Some cells become terminally differentiated. That means these cells are already in the final stage, they don’t divide or grow. These cells are muscle, cardiac and neuron cells. In the irreversible cells, some are senescent, which means cells become dormant, inactive due to certain stresses, like tissue remodeling, when there’s an injury, oxidative damage, and aging, these will lead the cells to senescent. During aging, there are certain cells that are related to age-related disorders, for example, in osteoarthritis, osteoclast, and osteoblast activities are changed, and it can cause problems in the body. So most of the age-related problems are due to this senescent. During biogenesis and tissue remodeling again you need some senescent cells for the proper development of embryo and tissue repair. Another thing is these malignant cells are very resistant to senescent, so then senescent work as a potent barrier to prevent the tumour genesis. If the cells exceed this controlled mechanism, they will become malignant cells.
- Some cells will be going into the G0 phase so they will no longer be inside the cell cycle they move to some sleeping position. Almost all cells in our body are differentiated cells that which are in G0 phase. Look at the G0 phase, they can be in the G0 phase temporary, or permanently. Depending on that we divide this G0 phase into two types. Reversible G0 and irreversible G0. The cells which are in the reversible G0 phase are, for example, hepatocytes, all the stem cells, (the pluripotent cells they become stem cellsand they are immature cells for other tissues). They are in a dormant stage, when necessary, they will come to the cell cycle and proliferate.. So, they are reversible. This shows some pictures of reversible cells. And there are some irreversible cells. Some cells become terminally differentiated. That means these cells are already in the final stage, they don’t divide or grow. These cells are muscle, cardiac and neuron cells. In the irreversible cells, some are senescent, which means cells become dormant, inactive due to certain stresses, like tissue remodeling, when there’s an injury, oxidative damage, and aging, these will lead the cells to senescent. During aging, there are certain cells that are related to age-related disorders, for example, in osteoarthritis, osteoclast, and osteoblast activities are changed, and it can cause problems in the body. So most of the age-related problems are due to this senescent. During biogenesis and tissue remodeling again you need some senescent cells for the proper development of embryo and tissue repair. Another thing is these malignant cells are very resistant to senescent, so then senescent work as a potent barrier to prevent the tumour genesis. If the cells exceed this controlled mechanism, they will become malignant cells.
- Let’s go to the S-phase of the cell cycle. This is where the DNA becomes uncoiled and duplicated and then all other additional organelles for the replication also will occur. This will ensure that each emerging daughter cell has the same genetic content as the mother
- From the G1 phase, cells come to the G2 phase or gap phase which occupies the time from the end of the S phase to the onset of mitosis, during this time cells prepare for mitosis by making all the proteins which are necessary for that. Example tubulin, proteins called tubulin are needed to make microtubules in the cell division to drag the chromosomes towards the home. This takes on average about one hour
- Then the M-phase where the cell division occurs, the nucleus will be replicated, and the cytoplasm will also be divided into producing genetically identical two daughter cells. Details in the M-phase will be learned from the next lecture in cell division and also somatic cells, mitosis in germ cells. To complete the stages here, mitotic phase devided in to prophase prometaphase, metaphase, anaphase, telophase, and cytokinesis. Prophase is the initial phase, next is the metaphase followd by anaphase where the chromatid separation occurs, telophase where these chromosomes move towards different poles, cytokinesis is the division of the cytoplasm. We will lear the events occur in the cell division in details during lecture on cell division
- Next is the cellcycle is regulation . If there is an abnormal DNA that is synthesis in the S-phase has to be corrected. We know that there are various correction methods available during DNA replication but still, there can be some problems, so it has to be corrected before it goes to the M-phase. There are two points where this correction occurs at, S-phase and then the G2-phase. And there can be problems even in the M-phase during the cell division so the new daughter cell might have some problems and that also will be checked in a certain phase before it goes to the G2, so there are some checkpoints. G1 checkpoint and then S checkpoint, G2 checkpoint and M checkpoint. For each and every phase before it passes to the next phase there is a checkpoint.
- As you are aware most of the cellular mechanisms are controlled by the phosphorization and dephosphorization of certain proteins. During the transcription-translation also there are certain proteins that are phosphorylated and become active. There are certain proteins that are dephosphorylated and become active. So, this phosphorylation and dephosphorylation are very important phenomena in these cellular mechanisms. You will learn in metabolism most of the enzymes become phosphorylated and activated. Similarly, when they become dephosphorylated, they inactivate. Phosphorylation and dephosphorylation play an important role in this cell cycle regulation. I want to show you here this p-53 is one of the protein which is protein binds to the transcription site it activates the transitional process it binds with the other proteins and then activates and this binding is favored by phosphorylation of the p-53, if not p-53 is not active. It is there but it is not active when it becomes phosphorylated it becomes active and the process occurs
- Other than these cyclin and cyclin-dependent kinases, there is an important one more protein which involves in this regulation, that MPF there are three names for this, M-phase promoting factor, or mitosis promoting factor, Maturation promoting factor. It is kinase as it can phosphorylate target proteins.
- So this MPF is activated at the end of the G2 by dephosphorylation by phosphatase, which removes the phosphate group which was added before. that can phosphorylate some other proteins which are involved in the cell cycle progression. So, there are various proteins The nuclear lamina depolymerizes causing it to disassemble which in turn causes the nuclear membrane to disassemble Histone H1 binds to the DNA in chromosomes, causing the chromosomes to condense Cytoskeletal proteins allow cytoskeletal filaments to assemble which leads to: Formation of the mitotic spindle which separates the daughter chromosomes formation of the cleavage furrow by microfilaments which allows cytokinesis (constricting the cell at the center) to occur resulting in the formation of two new cells