Cell Division & Cell Cycle - Cell Biology MD152 (PDF)

Cell Division & Cell Cycle Cell Biology MD152 Prof A. Stephanou Cell Division & Cell Cycle Control Dr A. Stephanou MD105 School of Medicine (EUC)  Objectives: To know why cells need to divide Understand the different phases of the cell di...

Cell Division & Cell Cycle Cell Biology MD152 Prof A. Stephanou Cell Division & Cell Cycle Control Dr A. Stephanou MD105 School of Medicine (EUC)  Objectives: To know why cells need to divide Understand the different phases of the cell division Know the different phase of the cell cycle Understand that defects in cell division and the cell cycle leads to diseases  Functions of Cell Division 100 µm 200 µm 20 µm (a) Reproduction. An amoeba, (b) Growth and development. (c) Tissue renewal. These dividing a single-celled eukaryote, is This micrograph shows a bone marrow cells (arrow) will dividing into two cells. Each sand dollar embryo shortly after give rise to new blood cells. new cell will be an individual the fertilized egg divided, forming organism. two cells.  Cell Division An integral part of the cell cycle Results in genetically identical daughter cells Cells duplicate their genetic material – Before they divide, ensuring that each daughter cell receives an exact copy of the genetic material, DNA  DNA Genetic information - genome Packaged into chromosomes Figure 12.3 50 µm  Phases of the Cell Cycle The cell cycle consists of – Interphase – normal cell activity – The mitotic phase – cell divsion INTERPHASE Growth (DNA synthesis) G1 Growth G2  Phases of the Cell Cycle Interphase – G1 - primary growth – S - genome replicated – G2 - secondary growth M - mitosis C - cytokinesis  Mitosis and Meiosis All normal cells have 46 chromosomes (diploid cells). These cells duplicate and divide to form daughter cells, with 46 chromosomes Process is called mitosis and can occur with most cells in the body  Meiosis Sex Cells - Gametes Unlike somatic cells, sperm and egg cells are haploid cells, containing only one set of chromosomes At sexual maturity the ovaries and testes produce haploid gametes by meiosis  What is Mitotic Cell Division? Division of mitotic cells (non reproductive cells) in eukaryotic organisms. - A single cell divides into two identical daughter cells - Daughter cells have same # of chromosomes as does parent cell.  Two Fundamental Cell Types Prokaryotic Prokaryotes cells/bacteria multiply by Binary fission Eukaryotic  Packing for the move… Protein complexes called condensins, help to promote chromosome to condense and prepare for duplication  Non- sister chromat ids Centromere Duplication Sister Sister chromatids chromatids Two unduplicated chromosomes Two duplicated chromosomes Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display.  Metaphase chromosome Centromere region of chromosome Kinetochore Kinetochore microtubules Sister Chromatids Copyright © The McGraw-Hill Companies, Inc. Permission required for reproduction or display. ⚫ The centromere is a constricted region of the chromosome containing a specific DNA sequence, to which is bound 2 discs of protein called kinetochores. ⚫ Kinetochores serve as points of attachment for microtubules that move the chromosomes during cell division:  Eukaryotic Cell Cycle 2 major phases: (3 stages) – DNA uncondensed (= chromatin) (4 stages + cytokinesis) - Nuclear division & division of cytoplasm – DNA condensed (= chromosomes)  Mitosis 1st – Prophase (chromosomes Condense) 2nd – Metaphase (chromosomes attach and align) 3rd – Anaphase (chromosome separate) 4th – Telophase and Cytokinesis (cell divides and chromosomes relax)  Mitotic Division of an Animal Cell METAPHASE ANAPHASE TELOPHASE AND CYTOKINESIS Metaphase plate Cleavage Nucleolus furrow forming Nuclear envelope Spindle Centrosome at Daughter forming one spindle pole chromosomes G2 of Interphase Two centrosomes have formed by replication of a single centrosome. In animal cells, each G2 OF INTERPHASE Centrosomes centrosome features two (with centriole pairs) Chromatin centrioles. (duplicated) Chromosomes, duplicated during S phase, cannot be seen individually because they have not yet condensed. Nucleolus Nuclear Plasma envelope membrane Prophase The chromatin fibers become more tightly coiled, condensing into discrete chromosomes observable with a light microscope. The nucleoli disappear. PROPHASE Each duplicated chromosome appears as two identical sister Aster Early mitotic chromatids joined together. spindle Centromere The mitotic spindle begins to form. It is composed of the centrosomes and the microtubules that extend from them. The radial arrays of shorter microtubules that extend from the centrosomes are called asters (“stars”). The centrosomes move away from each other, apparently propelled Chromosome, consisting by the lengthening microtubules of two sister chromatids between them. Metaphase Metaphase is the longest stage of mitosis, lasting about 20 minutes. The centrosomes are now at opposite ends of the cell. The chromosomes convene on the metaphase plate, an imaginary METAPHASE plane that is equidistant between Metaphase the spindle’s two poles. The plate chromosomes’ centromeres lie on the metaphase plate. For each chromosome, the kinetochores of the sister chromatids are attached to kinetochore microtubules coming from opposite poles. The entire apparatus of Spindle Centrosome at microtubules is called the spindle one spindle pole because of its shape. Telophase Two daughter nuclei begin to form in the cell. Nuclear envelopes arise from the fragments of the parent TELOPHASE AND CYTOKINESIS cell’s nuclear envelope and other portions of the Cleavage Nucleolus furrow forming endomembrane system. The chromosomes become less condensed. Mitosis, the division of one nucleus into two genetically identical nuclei, is now Nuclear complete. envelope forming  Cells divide at different rates. The rate of cell division varies with the need for those types of cells. Some cells are unlikely to divide (G0). Abnormalities of Cell Division May be due to chromosomal, genetic, or environmental factors, or combination of these – major chromosomal abnormalities usually lead to spontaneous abortion of fetus – chromosomal disorders are usually related to number or placement of chromosomes – chromosomes may fail to separate properly during cell division causing daughter cell to have an extra chromosome while other daughter cell has no chromosomes. – Abnormal number or structure of autosomal chromosomes is usually incompatible with life because these chromosomes carry a large number of essential genes. – Also a cause cancer- uncontrol cell proliferation! Part 2 Regulation of the Cell Cycle  The “cell cycle” The distinct events of the cell cycle are directed by a distinct cell cycle control system. These molecules trigger and coordinate key events in the cell cycle. The control cycle has a built-in clock, but it is also regulated by external adjustments and internal controls.  The “cell cycle” A checkpoint in the cell cycle is a critical control point where stop and go signals regulate the cycle. Three major checkpoints are found in the G1, G2, and M phases. Rhythmic fluctuations in the abundance and activity of control molecules pace the cell cycle. Some molecules are protein kinases that activate or deactivate other proteins by phosphorylating them. The levels of these kinases are present in constant amounts, but these kinases require a second protein, a cyclin, to become activated. Levels of cyclin proteins fluctuate cyclically. The complex of kinases and cyclin forms cyclin dependent kinases (Cdks). Cyclin-dependent Kinases (CDKs Cyclin Dependent Kinase Inhibitors (CKIs) cyclin dependent kinase inhibitors, CKIs – Selectively inhibit the kinase activity of CDKs by binding to complex of CDKs and cyclins – p21, p27, p16 anaphase-promoting complex, APC – is a complex of several proteins which is activated during mitosis to initiate anaphase. – The APC is an E3 ubiquitin ligase that marks target proteins, e.g. cyclinB and cyclinA, for degradation by the 26S proteasome. The irreversibility of proteolysis is utilized by cells to give the cell cycle directionality.  The “cell cycle” A variety of external chemical and physical factors can influence cell division. Growth factors: proteins released by one group of cells that stimulate other cells to divide. For example, platelet-derived growth factors (PDGF), produced by platelet blood cells, bind to tyrosine-kinase receptors of fibroblasts, a type of connective tissue cell. This triggers a signal-transduction pathway that leads to cell division. Each cell type probably responds specifically to a certain growth factor or combination of factors. Cyclin/CDK type control specific phases of the cell cycle  Three main checkpoints in the cell cycle 1. 1. Is cell the correct size? Is DNA damaged? 3. 2. Is DNA fully replicated? Is DNA damage repaired? 3. Have spindle fibers formed? Have they attached to 2. chromosomes correctly?  Checkpoint Control of Cell Cycle Cyclin-dependent kinases Cdk-G1 cyclin Cdk-Mitotic cyclin (MPF) Role of p53 in Cell Cycle Control (G1) Uncontrolled cell division - cancerous cells Many different types of cancers have mutations of the p53 regulatory protein  tumor suppressor genes – Tumor suppressor genes are normal genes that slow down cell division, repair DNA mistakes, and tell cells when to die (a process known as apoptosis or programmed cell death). When tumor suppressor genes don't work properly, cells can grow out of control, which can lead to cancer.  Cancer Cancer cells divide excessively and invade other tissues because they are free of the body’s control mechanisms. Cancer cells do not stop dividing when growth factors are depleted either because they manufacture their own, have an abnormality in the signaling pathway, or have a problem in the cell cycle control system. If and when cancer cells stop dividing, they do so at random points, not at the normal checkpoints in the cell cycle.  Why are cell cycle checkpoints important? Cancer Cancer Cells Evade One Major “Safety” Mechanisms Built into the Cell Cycle p53 protein normally targets cells with severe DNA damage to undergo programmed cell death. If the p53 gene is mutated, damaged cells will not be removed and may continue dividing in an uncontrolled manner.