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Edit Comment Close Premium member Presentation Transcript Cytogenetics Lec.7 : Cytogenetics Lec.7 Hussein Sabit, Ph.D Ready? : Ready? Begin! 4:00 : 4:00 Cell cycle is a common action performed by all dividable cell types. How it is being controlled? 3:00 : 3:00 What are the factors affecting the movement from phase to phase? 2:00 : 2:00 How can cell receive those messages? Is it sms or Bluetooth? 1:00 : 1:00 What will happen if a cell lost the ability to be controlled? Regulation of the cell cycle : Regulation of the cell cycle How cell division (and thus tissue growth) is controlled is very complex. The following terms are some of the features that are important in regulation, and places where errors can lead to cancer. Cancer is a disease where regulation of the cell cycle goes wrongly and normal cell growth and behavior is lost. 7 Hussein Sabit, Ph.D Slide 8: Cdk (cyclin dependent kinase, adds phosphate to a protein), along with cyclins, are major control switches for the cell cycle, causing the cell to move from G1 to S or G2 to M. p53 is a protein that functions to block the cell cycle if the DNA is damaged. If the damage is severe this protein can cause apoptosis (cell death). p53 levels are increased in damaged cells. This allows time to repair DNA by blocking the cell cycle. A p53 mutation is the most frequent mutation leading to cancer. 8 Hussein Sabit, Ph.D Cyclins : Cyclins Cyclins are named such because they undergo a constant cycle of synthesis and degradation during cell division. When cyclins are synthesized, they act as an activating protein and bind to Cdks forming a cyclin-Cdk complex. This complex then acts as a signal to the cell to pass to the next cell cycle phase. Eventually, the cyclin degrades, deactivating the Cdk, thus signaling exit from a particular phase. There are two classes of cyclins: mitotic cyclins and G1 cyclins. 9 Hussein Sabit, Ph.D G1 cyclins : G1 cyclins G1 cyclins bind to Cdk proteins during G1. Once bound and activated, the Cdk signals the cell's exit from G1 and entry into S phase. When the cell reaches an appropriate size and the cellular environment is correct for DNA replication, the cyclins begin to degrade. G1 cyclin degradation deactivates the Cdk and leads to entry into S phase. 10 Hussein Sabit, Ph.D Mitotic Cyclins : Mitotic Cyclins Mitotic cyclins accumulate gradually during G2. Once they reach a high enough concentration, they can bind to Cdks. When mitotic cyclins bind to Cdks in G2, the resulting complex is known as Mitosis-promoting factor (MPF). This complex acts as the signal for the G2 cell to enter mitosis. Once the mitotic cyclin degrades, MPF is inactivated and the cell exits mitosis by dividing and re- entering G1. 11 Hussein Sabit, Ph.D What is the Checkpoint? : What is the Checkpoint? The cell cycle proceeds by a defined sequence of events where late events depend upon completion of early events. The aim of the dependency of events is to distribute complete and accurate replicas of the genome to daughter cells. To monitor this dependency, cells are equipped with the checkpoints that are set at various stages of the cell cycle. When cells have DNA damages that have to be repaired, cells activate DNA damage checkpoint that arrests cell cycle. According to the cell cycle stages, DNA damage checkpoints are classified into at least 3 checkpoints: G1/S (G1) checkpoint, intra-S phase checkpoint, and G2/M checkpoint. 12 Hussein Sabit, Ph.D Slide 13: Upon perturbation of DNA replication by drugs that interfere with DNA synthesis, DNA lesions, or obstacles on DNA, cells activate DNA replication checkpoint that arrests cell cycle at G2/M transition until DNA replication is complete. There are more checkpoints such as Spindle checkpoint and Morphogenesis checkpoint. The spindle checkpoint arrests cell cycle at M phase until all chromosomes are aligned on spindle. This checkpoint is very important for equal distribution of chromosomes. Morphogenesis checkpoint detects abnormality in cytoskeleton and arrests cell cycle at G2/M transition. Hussein Sabit, Ph.D 13 Slide 14: 14 Hussein Sabit, Ph.D Slide 15: 15 Hussein Sabit, Ph.D Cell Cycle Checkpoints : Cell Cycle Checkpoints G1/S Monitors cell size and for DNA damage G2/M Replication complete, DNA damage? M Spindle fibers connected, etc.? G0 Does body require more of my type of cell? 16 Hussein Sabit, Ph.D Activation of CDKs : Activation of CDKs 17 Hussein Sabit, Ph.D G1 (Restriction) Checkpoint : G1 (Restriction) Checkpoint The first checkpoint is located at the end of the cell cycle's G1 phase, just before entry into S phase, making the key decision of whether the cell should divide, delay division, or enter a resting stage. Many cells stop at this stage and enter a resting state called G0. Liver cells, for instance, only enter mitosis around once or twice a year. The G1 checkpoint is where eukaryotes typically arrest the cell cycle if environmental conditions make cell division impossible or if the cell passes into G0 for an extended period. In animal cells, the G1 phase checkpoint is called the restriction point. 18 Hussein Sabit, Ph.D G2 Checkpoint : G2 Checkpoint The second checkpoint is located at the end of G2 phase, triggering the start of the M phase (mitosis). In order for this checkpoint to be passed, the cell has to check a number of factors to ensure the cell is ready for mitosis. If this checkpoint is passed, the cell initiates the many molecular processes that signal the beginning of mitosis. The CDKs associated with this checkpoint are activated by phosphorylation of the CDK by the action of a "Maturation promoting factor" (or Mitosis Promoting Factor, MPF). The MPF activates the CDK in response to environmental conditions being right for the cell and allows the cell to begin DNA replication. 19 Hussein Sabit, Ph.D Metaphase Checkpoint : Metaphase Checkpoint The mitotic spindle checkpoint occurs at the point in metaphase where all the chromosomes have/should have aligned at the mitotic plate and be under bipolar tension. 20 Hussein Sabit, Ph.D What happens if you lose one of checkpoints? : What happens if you lose one of checkpoints? DNA replication and chromosome distribution are indispensable events in the cell cycle control. Cells must accurately copy their chromosomes, and through the process of mitosis, segregate them to daughter cells. The checkpoints are surveillance mechanism and quality control of the genome to maintain genomic integrity. Checkpoint failure often causes mutations and genomic arrangements resulting in genetic instability. Genetic instability is a major factor of birth defects and in the development of many diseases, most notably cancer. Therefore, checkpoint studies are very important for understanding mechanisms of genome maintenance as they have direct impact on the ontogeny of birth defects and the cancer biology. 21 Hussein Sabit, Ph.D Slide 22: The process of asexual reproduction begins after a sperm fertilizes an egg. Three reasons why cells reproduce by asexual reproduction: 1. Growth 2. Repair 3. Replacement : Three reasons why cells reproduce by asexual reproduction: 1. Growth 2. Repair 3. Replacement Skin cancer - the abnormal growth of skin cells - most often develops on skin exposed to the sun. Cell that reproduce by asexual reproduction reproduce constantly. Slide 24: The process of asexual reproduction begins after a sperm fertilizes an egg. Three reasons why cells reproduce by asexual reproduction: 1. Growth 2. Repair 3. Replacement : Three reasons why cells reproduce by asexual reproduction: 1. Growth 2. Repair 3. Replacement Skin cancer - the abnormal growth of skin cells - most often develops on skin exposed to the sun. Cell that reproduce by asexual reproduction reproduce constantly. Slide 26: Interphase Prophase Metaphase Anaphase Telophase & Cytokinesis Interphase occurs before mitosis begins : Interphase occurs before mitosis begins Chromosomes are copied (# doubles) Chromosomes appear as threadlike coils (chromatin) at the start, but each chromosome and its copy(sister chromosome) change to sister chromatids at end of this phase CELL MEMBRANE Nucleus Cytoplasm Interphase : Interphase Animal Cell Plant Cell Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm Prophase 1st step in Mitosis : Prophase 1st step in Mitosis Mitosis begins (cell begins to divide) Centrioles (or poles) appear and begin to move to opposite end of the cell. Spindle fibers form between the poles. Centrioles Sister chromatids Spindle fibers Prophase : Prophase Animal Cell Plant Cell Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm Spindle fibers Centrioles Metaphase 2nd step in Mitosis : Metaphase 2nd step in Mitosis Chromatids (or pairs of chromosomes) attach to the spindle fibers. Centrioles Spindle fibers Metaphase : Metaphase Animal Cell Plant Cell Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm Anaphase 3rd step in Mitosis : Anaphase 3rd step in Mitosis Chromatids (or pairs of chromosomes) separate and begin to move to opposite ends of the cell. Centrioles Spindle fibers Anaphase : Anaphase Animal Cell Plant Cell Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm Telophase 4th step in Mitosis : Telophase 4th step in Mitosis Two new nuclei form. Chromosomes appear as chromatin (threads rather than rods). Mitosis ends. Nuclei Nuclei Chromatin Telophase : Telophase Animal Cell Plant Cell Photographs from: http://www.bioweb.uncc.edu/biol1110/Stages.htm Cytokinesisoccurs after mitosis : Cytokinesisoccurs after mitosis Cell membrane moves inward to create two daughter cells – each with its own nucleus with identical chromosomes. Slide 38: Animal Mitosis -- Review Slide 39: Plant Mitosis -- Review REMEMBER! : REMEMBER! Interphase Prophase Metaphase Anaphase Telophase Cytokinesis I Pay More Attention To Cats Cell Cycle : 41 Cell Cycle Slide 42: Thanks 4 paying Attention !!! 42 Hussein Sabit, Ph.D You do not have the permission to view this presentation. In order to view it, please contact the author of the presentation.