Mol bio lecture 3.pdf

1. List the sequential phases of mitosis and describe the major events of each phase Mitosis is the process by which a eukaryotic cell divides its nucleus, leading to the formation of two identical daughter cells. The sequential phases of mitosis are: 1. Prophase: ○ Chromatin Condensati...

1. List the sequential phases of mitosis and describe the major events of each phase Mitosis is the process by which a eukaryotic cell divides its nucleus, leading to the formation of two identical daughter cells. The sequential phases of mitosis are: 1. Prophase: ○ Chromatin Condensation: The chromatin fibers condense into visible chromosomes, each consisting of two sister chromatids joined at the centromere. ○ Nucleus: Nucleus remains in tact ○ Spindle Formation: The mitotic spindle, composed of microtubules, begins to form, emanating from the centrosomes (which have duplicated during interphase). 2. Prometaphase: ○ Nuclear Envelope Disappears: The nuclear envelope is fully broken down. ○ Chromosome Attachment: ALL Spindle fibers attach to the kinetochores, protein structures at the centromeres of the chromosomes. ALL MUST ATTACH ○ Chromosome Movement: The chromosomes begin moving towards the metaphase plate, an imaginary plane equidistant between the two poles of the cell. 3. Metaphase: ○ Chromosome Alignment: ALL chromosomes align at the metaphase plate, with their centromeres positioned at the center. ○ Spindle Checkpoint: The cell ensures that all chromosomes are properly attached to spindle fibers from opposite poles, which is crucial for the equal distribution of genetic material. 4. Anaphase: ○ Chromatid Separation: The centromeres split, and the sister chromatids (now individual chromosomes) are pulled apart toward opposite poles of the cell by the shortening of spindle fibers. ○ Cell Elongation: The cell elongates as the microtubules not attached to chromosomes push against each other, further separating the poles. 5. Telophase: ○ Chromosome Decondensation: The separated chromosomes reach the opposite poles and begin to decondense back into chromatin.  ○ Nuclear Envelope Reformation: A new nuclear envelope forms around each set of chromosomes, resulting in the formation of two nuclei. ○ Spindle Disassembly: The spindle apparatus disassembles as its role in mitosis is complete. 6. Cytokinesis (Not a phase of mitosis but closely associated): ○ Cytoplasmic Division: The cytoplasm divides, resulting in two separate daughter cells, each with a complete set of chromosomes. This process is different in animal cells (involving a cleavage furrow) and plant cells (involving the formation of a cell plate). 2.Assess the consequence for chromosome separation for changes in activity for the key players of regulation in the checkpoint Metaphase checkpoint - Alignment is driven by kinetochore attachment and positioning. - A single unattached kinetochore presents a strong enough signal to stall mitosis - driven by the anaphase promoting complex. Cohesin - Multi-subunit protein complex - Maintains adhesion until anaphase; holds sister chromatids together at the metaphase plate Sister Chromatid Separation 1. Cohesion holds sister chromatids together at the metaphase plate until anaphase 2. APC bind CDC20 to become active 3. Active APC degrades securin 4. Degradation of securin frees separase 5. Free separase cleaves cohesin 6. Allows sister chromatids to separate Rate Limiting Steps: - CDC20 synthesis - APC Phosphorylation Consequences of APC Activation - APC activation degrades securin, allowing separase to cleave cohesin and sister chromatids to separate - APC activation also leads to the cleavage and inactivation of m-phase cyclin - Initiates synthesis of G1 cyclin Spindle Attachment Checkpoint - Checks to ensure that all chromosomes are properly attached to the spindle before separation occurs - A single unattached kinetochore is sufficient to prevent the activity of all the CDC20 molecules in a cell and stall mitosis in Metaphase - MAD2 sequesters CDC20 and is recruited to unattached kinetochores ◦Explain the steps of the Anaphase Checkpoint 3.Assess consequences for errors in major events of each phase of mitosis and meiosis ◦Determine the stage at which a cell would stall based on the error described 1. Errors in Mitosis a. Prophase Errors: Error Type: Failure to condense chromosomes properly or incorrect spindle formation. Consequence: Incomplete or faulty chromosome segregation. Stalling Point: The cell might stall at the G2/M checkpoint if the chromosomes are not properly condensed or if spindle formation is defective, as the cell monitors whether all components are ready for mitosis. b. Metaphase Errors: Error Type: Improper alignment of chromosomes at the metaphase plate or incorrect attachment of spindle fibers to kinetochores. Consequence: Aneuploidy, where daughter cells have an incorrect number of chromosomes, leading to conditions like cancer or developmental disorders. Stalling Point: The cell would stall at the metaphase checkpoint (also known as the spindle assembly checkpoint) if all chromosomes are not correctly aligned and attached to the spindle fibers, preventing anaphase from initiating. c. Anaphase Errors: Error Type: Failure to properly separate sister chromatids. Consequence: One daughter cell may receive both chromatids of a chromosome, while the other receives none, resulting in aneuploidy. Stalling Point: If the spindle fibers fail to pull the chromatids apart, the cell may attempt to correct this; however, if the error persists, it may undergo apoptosis or lead to cancerous growth if the cell cycle continues unchecked. d. Telophase/Cytokinesis Errors: Error Type: Incomplete reformation of the nuclear envelope or failure of cytokinesis. Consequence: Multinucleated cells or cells with incomplete sets of chromosomes, leading to cellular dysfunction. Stalling Point: The cell might not stall but proceed with defective cytokinesis, resulting in abnormal daughter cells. However, significant issues might trigger a post-mitotic checkpoint leading to apoptosis. ◦Determine the consequence for chromosome separation and function of daughter cells if errors in the anaphase promoting complex or corresponding players in the checkpoint are altered 4.Understand the complexity of cytokinesis and the importance of the cytoskeleton to the overall process of cell division and explain the relationship between cytokinesis and embryogenesis (morphogenesis and motility*) ◦Summarize the features of cytokinesis and the steps necessary for cytokinesis to occur properly Summary of Cytokinesis Features and Necessary Steps Cytokinesis Features: Final Step in Cell Division: Cytokinesis is the process that physically divides the cytoplasm of a parental cell into two daughter cells after mitosis or meiosis. Involves Cytoskeletal Components: The actin and myosin filaments of the cytoskeleton form a contractile ring at the cell's equator, which tightens to pinch the cell into two. Asymmetric vs. Symmetric Division: Cytokinesis can be symmetric, producing two equal daughter cells, or asymmetric, leading to cells of different sizes and contents, particularly important in development. Steps Necessary for Proper Cytokinesis:  1. Formation of the Contractile Ring: In early telophase, Signals, such as Rho-GEF and Ect-2, determine the positioning of the ring at the equator and send negative signals to the poles. Microtubules move centralspindlin complex to the equator. 2. Contraction of the Contractile Ring: In mid telophase, Actin and Myosin motor proteins tighten the ring and create a cleavage furrow that deepens to split the cell. Contractile forces generated at the cleave furrow bring the plasma membrane together 3. Cleavage Furrow Formation: Actin and Microtubules lay down the highway for cellular components and position of the furrow allows for evenly split cells. The cleavage furrow continues to deepen until the cell is pinched into two separate cells. 4. Final Separation: In late telophase, The midbody ring, a structure at the center of the dividing cell, coordinates the final separation, or abscission, of the daughter cells. 5. Proper Distribution of Organelles and Cytoplasm: During cytokinesis in somatic mitosis, the organelles and cytoplasm are perfectly split in half to ensure both daughter cells are viable. ◦Identify the differences in cytokinesis observed during embryogenesis Cytokinesis In typical somatic mitosis - the division is nearly perfectly in half with each daughter cell receiving half the cytoplasmic contents Cytokinesis In embryogenesis - asymmetrical cell divisions are possible enabling concentration of materials into one of the two daughter cells generating concentration gradients - Polarity proteins and Rho-GTPases play a role in this process - enables the development of cells that are unique in materials and gene expression, affecting cell fate - Part of morphogenesis and specialization of cell type ◦Link changes in distribution of cytoplasmic contents with morphogenesis