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Lec.12 Dr:Buthaina Al-Sabawi Date:21/12/2016 The Cell Cycle The cell cycle, is the series of events that leads to duplication and division of a cell. Division cycle consists of 4 coordinated processes:(1) cell growth,(2) DNA replication, (3)distribution of the duplicated chromosomes ,(4) cell division. The alternation between mitosis and interphase called cell cycle. Cell cycle divided into 2 stages, (Mitosis and interphase). Mitosis(4 stages) (1)Prophase (2) Metaphase (3) Anaphase (4) Telophase (1) Interphase: Before a cell can enter cell division, it needs to take in nutrients. All of the preparations are done during interphase. Interphase is a series of changes that takes place in a newly formed cell and its nucleus, before it becomes capable of division again. It is also called preparatory phase or intermitosis. Previously it was called resting stage because there is no apparent activity related to cell division. Typically interphase lasts for at least 90% of the total time required for the cell cycle. Interphase, is itself divided into three phases (1). G1 (Growth phase) (2). S (DNA synthesis) (3). G2 (Post DNA duplication) The cell cycle divided into four periods, G1, S, G2 and mitosis (M) G1:(Gap1): The first gap in the normal cell cycle is called G1 and is the period when the necessary proteins for DNA replication are synthesized. The cell grow in size and the cellular organelles increase in number (such as mitochondria, ribosomes), and grows in size, the cell is metabolically active & continuously grows but does not replicate it’s DNA. (S): is referred as synthesis phase when DNA synthesis. During duplication, each chromosome doubles to produce identical sister chromatids, and also centrioles replicate take place. G2: (Gap2) is the internal between chromosome duplication and the beginning of mitosis, during which cell growth continues and proteins are synthesized in preparation for mitosis. The duration of the cell cycle phases varies considerably in different kinds of cells. (2) In bone tissue, G1 lasts 25 h. The S phase (DNA synthesis) lasts about 8 h. The G2-plus-mitosis phase lasts 2.5-3 h. Mitosis is the process by which a eukaryotic cell separates the chromosomes in its cell nucleus into two identical sets in two nuclei. During the process of mitosis the pairs of chromosomes condense and attach to fibers that pull the sister chromatids to opposite sides of the cell. Cell cycle activities may be temporarily or permanently suspended in a G0 phase. Some cells, such as skin cells, divide continuously throughout the life of the organism. Other cells, such as skeletal muscle cells and nerve cells, are arrested in the G1 stage. Cardiac muscle cells are arrested in the G2-stage. The division cycle is regulated by extracellular signals from the environment (nutrient, size of cell, growth factors). Growth factors: are molecules that attach to the plasma membrane receptors and thereby bring about cell growth. Availability of Growth factors controls the animal cell cycle at a point in the late G1 called the restriction point. If growth factors are not available during G1, the cells enter in a rest stage of the cycle (G0). GF,is a naturally occurring substance capable of stimulating cellular growth, proliferation, healing, and cellular differentiation. Usually it is a protein or a steroid hormone. Growth factors are important for regulating a variety of cellular processes. Growth factors typically act as signaling molecules between cells. Examples are cytokines and hormones that bind to specific receptors on the surface of their target cells. (3) They often promote cell differentiation and maturation, which varies between growth factors. For example, bone morphogenetic proteins stimulate bone cell differentiation, while fibroblast growth factors and vascular endothelial growth factors stimulate blood vessel differentiation. Classes of growth factors There are many families, some of which are listed below: Bone morphogenetic proteins (BMPs) Colony-stimulating factors o Macrophage colony-stimulating factor (M-CSF) o Granulocyte colony-stimulating factor (G-CSF) o Granulocyte macrophage colony-stimulating factor (GM-CSF) Epidermal growth factor (EGF) Erythropoietin (EPO) Fibroblast growth factor (FGF) Foetal Bovine Somatotrophin (FBS) (4) Growth differentiation factor-9 (GDF9) Hepatocyte growth factor (HGF) Insulin-like growth factors o Insulin-like growth factor-1 (IGF-1) o Insulin-like growth factor-2 (IGF-2) Interleukins Keratinocyte growth factor (KGF) Migration-stimulating factor (MSF) Macrophage-stimulating protein (MSP o Brain-derived neurotrophic factor (BDNF) o Nerve growth factor (NGF) Placental growth factor (PGF) Platelet-derived growth factor (PDGF) T-cell growth factor (TCGF) Thrombopoietin (TPO) Transforming growth factors coordination between different phases of cell cycle is dependent on a system of checkpoints and feedback controls that prevent entry into the next phase of the cell cycle until the events of the preceding phase have been completed. Several cell cycle checkpoints function to ensure that incomplete or damaged chromosome are not replicated and passed on to the daughter cells. (5) The cell cycle is highly regulated, and checkpoints control transitions between cell- cycle stages. Checkpoints are biochemical circuits that detect external or internal problems and send inhibitory signals to the cell-cycle system. There are four major types of checkpoints. The restriction point. DNA damage checkpoints. DNA replication checkpoints. Spindle assembly checkpoints (also called metaphase checkpoints). Checkpoint regulation plays an important role in an organism's development. In sexual reproduction, when egg fertilization occurs, when the sperm binds to the egg, it releases signaling factors that notify the egg that it has been fertilized. Among other things, this induces the now fertilized oocyte to return from its previously dormant, G0, state back into the cell cycle and on to mitotic replication and division. (6)