L7-8-%20CELLULAR%20REPRUDUCTION,%20CELL%20CYCLE%20AND%20MITOSIS_fffae3630056eeaf.pdf

Cellular Reproduction Cell Cycle Eukaryotic cell cycle and the events of interphase Regulation and importance of cell cycle check points Mitosis Phases of mitosis Cytokinesis  Learning Objectives We begin with an overview of the events that take plac...

Cellular Reproduction Cell Cycle Eukaryotic cell cycle and the events of interphase Regulation and importance of cell cycle check points Mitosis Phases of mitosis Cytokinesis  Learning Objectives We begin with an overview of the events that take place during a typical cell cycle. We then describe the complex system of regulatory proteins called the cell-cycle control system, which orders and coordinates these events to ensure that they occur in the correct sequence. We next discuss in detail the major stages of the cell cycle, in which the chromosomes are duplicated and then segregated into the two daughter cells. At the end how animals use extracellular signals to control the survival, growth, and division of their cells. These signaling systems allow an animal to regulate the size and number of its cells—and, ultimately, the size and form of the organism itself.  (1) How do cells duplicate their contents—including the chromosomes, which carry the genetic information? (2) How do they participate the duplicated content and split into two? (3) How do they coordinate all the steps and machinery required for these two processes?  Cellular Reproduction Alll cells come from cells Life in humans begins a a single cell Cellular reproduction involves 2 processes: growth andcell division - A cellduplicates its contents (organelles, DNA) during growth - During celldivision, cellularcontents andDNA of the parent cell are distributed to the daughter cells Eukaryotic Cell Cycle Cell Cycle overview  The Cell Cycle The sequence of events that occur in fairly rapidly dividing (proliferating) mammalian cells The most basic function of the cell cycle is to duplicate accurately the vast amount of DNA in the chromosomes and then segregate the copies precisely into two genetically identical daughter cells The cell-cycle control system ensures that the various events of the cycle take place in the correct sequence and at the correct time  The Cell Cycle Definition The cell cycle is the sequence of stages through which a cell passes from one cell division to the next. During the cell cycle the cell – Grows – Duplicates its DNA – And divides to form a new cell The Cell Cycle Cells reproduce by duplicating their contents and dividing in two, a process called the cell cycle. For simplicity, we use a hypothetical eukaryotic cell—with only one copy each of two different chromosomes—to illustrate how each cell cycle produces two genetically identical daughter cells. Each daughter cell can divide again by going through another cell cycle, and so on for generation after generation The Cell Cycle The duration of the cell cycle varies greatly from one cell type to another. In an early frog embryo, cells divide every 30 minutes, whereas a mammalian fibroblast in culture divides about once a day Phases of the Cell Cycle The Cell Cycle Phases of the Cell Cycle G1 phase – gap between M and S phase S phase – DNA replicates G2 phase – between S and M phase M phase – nucleus divides (mitosis) and cytoplasm divides (cytokinesis) The Cell Cycle The period between one M phase and the next is called Interphase. during which the cell replicates its DNA, transcribes genes, synthesizes proteins and increases in size it encompasses the remaining three phases of the cell cycle S phase (S = synthesis), the cell replicates its DNA. two ―gap” phases—called G1 and G2—during which the cell continues to grow. Together with S phase, G1 and G2 provide the time needed for the cell to grow and duplicate its cytoplasmic organelles.  G1 is an important point of decision-making for the cell. During the gap phases, the cell monitors both its internal state and external environment. This monitoring ensures that conditions are suitable for reproduction and that preparations are complete before the cell commits to the major upheavals of S phase (which follows G1) and mitosis (following G2). At particular points in G1 and G2, the cell decides whether to proceed to the next phase or pause to allow more time to prepare. The Cell Cycle The two most dramatic events in the cell cycle are in M phase (Division Phase) Mitosis when the nucleus divides Cytokinesis when the cell later splits in two Regulation and Importance of Cell Cycle Check Points The Cell-Cycle Control System  A Cell-Cycle Control System Triggers the Major Processes of the Cell Cycle To ensure that they replicate all their DNA and organelles, and divide in an orderly manner, eukaryotic cells possess a complex network of regulatory proteins known as the cell-cycle control system.  Control of the Cell Cycle If it wasn't controlled, your cells would continue to grow and divide...over and over again! A number of proteins regulate and control the cell cycle. Tell the cell when is the proper time to grow and divide, Stop the cell when the time's not right. Clinically, cancer can be described as uncontrolled cell growth and proliferation Understanding cell cycle control has many implications  Cell Cycle Control Cell cycle machinery is subordinate to a cell cycle control system The control system consists mainly of protein complexes These complexes consist of – Cyclin subunit and – Cdk (cyclin dependent kinase) subunit  Cell Cycle Control A Cdk must bind a regulatory protein called a cyclin before it can become enzymatically active. This activation also requires an activating phosphorylation of the Cdk. Once activated, a cyclin–Cdk complex phosphorylates key proteins in the cell that are required to initiate particular steps in the cell cycle. The cyclin also helps direct the Cdk to the target proteins that the Cdk phosphorylates. Figure 1. The cell cycle phases and their associated cyclin-dependent kinases (CDK)/cyclin complexes. In the G1 phase of the cell cycle, the synthesis of cyclin D is increased. This cyclin partners with CDK4/6 to promote cell cycle entry, and its progression through G1, as well as the G1/S transition. During the S phase, CDK2 in complex with cyclin A controls the phosphorylation of targets involved in DNA replication. Cyclin A is found highly expressed in this phase and until the last stages of G2. In the G2 phase, the primary regulator of the cell cycle is CDK1.  Cell Cycle Control Cyclin has regulatory function Cdk catalytic function Cdk expression is constant, but cyclin concentrations rise and fall at specific times in the cell cycle The Cdks are cyclically activated by cyclin binding and by phosphorylation status Once activated, Cdks phosphorylate key proteins in the cell  Cell Cycle Control The phosphorylation reactions that control the cell cycle are carried out by a specific set of protein kinases, while dephosphorylation is performed by a set of protein phosphatases.  CONTROL OF THE CELL CYCLE In most cells there are several points in the cell cycle, called checkpoints, at which the cycle can be arrested if previous events have not been completed Three checkpoints: G1/S cell cycle checkpoint G2/M DNA damage checkpoint Mitosis checkpoint  The cell-cycle control system regulates progression through the cell cycle at three main transition points G2/M DNA damage Mitosis checkpoint checkpoint G1/S cell cycle checkpoint The cell-cycle control system ensures that key processes in the cycle occur in the proper sequence. The cell cycle control system is shown as a controller arm that rotates clockwise, triggering essential processes when it reaches particular transition points on the outer dial. These processes include DNA replication in S phase and the segregation of duplicated chromosomes in mitosis. The control system can transiently halt the cycle at specific transition points—in G1, G2, and M phase— if extracellular or intracellular conditions are unfavorable. At the transition from G1 to S phase, the control system confirms that the environment is favorable for proliferation before committing to DNA replication. Cell proliferation in animals requires both sufficient nutrients and specific signal molecules in the extracellular environment; if these extracellular conditions are unfavorable, cells can delay progress through G1 and may even enter a specialized resting state known as G0 (G zero). In animals, the transition from G1 to S phase is especially important as a point in the cell cycle where the control system is regulated. Signals from other cells stimulate cell proliferation when more cells are needed—and block it when they are not.  G1 is an important point of decision-making for the cell. Based on intracellular signals that provide information about the size of the cell and extracellular signals reflecting the environment, the cell-cycle control machinery can either hold the cell transiently in G1 (or in a more prolonged nonproliferative state, G0), or allow it to prepare for entry into the S phase of another cell cycle.  G2/M -DNA damage checkpoint The G2/M DNA damage checkpoint prevents the cell from entering mitosis (M phase) if the genome is damaged It also checks if the cell is big enough (i.e. has the resources to undergo mitosis) Almost exclusively, internally controlled  At the transition from G2 to M phase, the control system confirms that the DNA is undamaged and fully replicated, ensuring that the cell does not enter mitosis unless its DNA is intact.  M checkpoint The M checkpoint is where the attachment of the spindle fibres to the centromeres is assessed. Only if thisis correct can mitosis proceed. Failure to attach spindle fibres correctly would lead to failure to separate chromosomes  Finally, during The mitosis, cell-cycle control machinery ensures that the duplicated chromosomes are properly attached to a cytoskeletal machine, called the mitotic spindle, before the spindle pulls the chromosomes apart and segregates them into the two daughter cells The Cell-Cycle Control System Can Pause the Cycle in Various Ways  The Cell-Cycle Control System Can Pause the Cycle in Various Ways The cell-cycle control system uses various mechanisms to pause the cycle at specific transition points. the control system uses a combination of the mechanisms. At the G1-to-S transition, it uses Cdk inhibitors to keep cells from entering S phase and replicating their DNA At the G2-to-M transition, it  Cell Cycle Control The essential processes ofSystem cell cycle, such as DNA replication, mitosis and cytokinesis is triggered by cell cycle control system. Network of regulatory proteins that governs progression of a eukaryotic cell through the cell cycle. A Clock is running within the cell - of synthesis and degradation of cyclins - which activate cyclin-dependant kinases (Cdk’s), which activate other proteins to cause checkpoint transitions. Cyclins must be destroyed at appropriate time for the cell cycle to progress normally M-cyclin combines with a M-kinase and initiates mitosis mitosis -promoting factor (MPF) MPF controls G2 → M by phosphorylating and activating proteins involving in: S-cyclin must combine with S-kinase for Chromosome condensation Nuclear envelope breakdown the cell cycle to begin DNA replication Spindle assembly It’s own self-destruction Cell-Cycle Progression Can Be Studied in Various Ways  Cell-Cycle Progression Can Be Studied in Various Ways Another way to assess the stage that a cell has reached in the cell cycle is by measuring its DNA content, which doubles during S phase. This approach is greatly facilitated by the use of DNA- binding fluorescent dyes and a flow cytometer, which allows large numbers of cells to be analyzed rapidly and automatically. Flow cytometry: to determine the lengths of G1, S, and G2 + M phases, by following over time a population of cells that have been preselected to be in one particular phase of the cell cycle: DNA content measurements on such a synchronized population of cells reveal how the cells progress through the cycle. DIVISION PHASE M phase Mitosis Cytokinesi s  Division Phase M Phase (Mitosis and Cytokinesis) – Parent cell divides to form two identical daughter cells – Mitosis can be divided into 5 stages –Prophase –Prometaphase –Metaphase –Anaphase –Telophase  Chromatid Chromatin + DNA Sister chromatid Homologous Centromere Chromosome Chromosome 62  A. Mitosis: is usually include five sub-phases: ❖ Prophase, ❖ Prometaphase, ❖ Metaphase, ❖ Anaphase, ❖ Telophase. By late interphase (G2), the chromosomes have been duplicated but are loosely packed. The centrosomes have been duplicated and begin to organize microtubules into an aster "star"  Prophas e First phase in mitosis. Duplicated chromosomes condense by thickening and shortening. Centrioles move to opposite poles (ends) of the cell. Centrioles are small protein bodies found in the cytoplasm that provides attachment for spindle fibres during cell division. Spindle fibres are protein structures that guide chromosome movement during cell division. Spindle fibres attach to centromeres of duplicated chromosomes to help them move. Nuclear membrane that surround the nucleus starts to dissolve.  Prometaphas The nucleare envelope fragments and microtubules from one pole attach to one of two kinetochores (special regions of the centromere) while microtubules from the other pole attach to the other kinetochore Metaphase Third phase of mitosis. Chromosomes move to the center of the cell. This center area is called the equatorial plate. Nuclear membrane completely dissolves. Anaphase Fourth phase of mitosis. Centromeres divide and sister chromatids separate. The sister chromatids are referred to a chromosomes now that they are separated. Chromosomes start to move to opposite poles of the cell. Telophas e Fourth and last stage of mitosis. Chromosomes reach opposite poles of the cell and begin to lengthen. Spindle fibres dissolve. Nuclear envelopes start to form around each mass of chromosomes. Cytokinesis Cytokinesis (division of the cytoplasm) typically follows mitosis. Cytokinesis is the splitting of the cytoplasm between the two masses of chromosomes to form two separate cells. Contraction of the cell pinches the cell into two new cells  Cell Cycle Interphase Division process Mitosis Cytokinesis G1 S G2 Prophase Prometaphase Metaphase Anaphase Telophase 77  Division is Differ Among Cells Cells have an internal biological clock determining how many times a cell can divide before it dies. Depending on the type of cell, some undergo more mitosis than others Liver cells divide when needed (damage repair). Nerve cells, heart and muscle cells do not divide at all. Skin cells divide frequently, are being damaged and dying off on a regular basis, so they are able to divide more than specialized cells.