Part 5 final exam The cell cycle and its control Countless divisions of a single celled zygote produce a cellular complex organism Cell division doesn t stop with formation of a mature organism continues throughout its life 25 million cells undergo division each second in an adult human replacing cells that have aged or died Mothers and daughters o Each diving cell is called a mother cell and its descendants are daughter cells o A mother cell transmits copies of its genetic information to its daughter cells which become the next cell generation o The cell cycle starts with cell division and ends with daughter cell formation or death the stages through which a cell passes constitute the cell cycle Phases of the cell cycle o 1 M phase mitotic Mitosis separation of chromosomes nuclear division Only a small percent of cells in a tissue cell culture is in mitosis at any given time Macromolecular synthesis is relatively inactive during mitosis 5 stages of Mitosis o Prophase o Metaphase o Anaphase o Telophase Cytokinesis cytoplasmic division into 2 daughter cells cell division Includes anaphase and telophase o 2 Interphase occupies bulk of the cycle hours days weeks or longer depending on cell type and conditions Preparations for upcoming mitosis occur Replication of cell s DNA Cell grows in volume Cell does active metabolic functions glucose oxidation replication transcription translation Divided into G1 first gap phase o Most variable stage o Most cells that have stopped dividing temporarily or permanently stop before initiation of DNA synthesis in a special G1 state called G0 Cells exit from cycle in G1 and are held in G0 where they continue to perform functions but don t divide o Cells must generate an internal signal to go from G0 or G1 to S S Phase DNA synthesis G2 second gap phase Cell cycles in vivo living organisms o 3 broad categories of cells 1 Cells with extreme structural specialization have lost the ability to divide nerve muscle RBCs Once differentiated they remain in that state until they die 2 Cells that normally do not divide but with the right stimuli make DNA and divide Liver cells induced to divide if surgically remove part of the liver Lymphocytes divide when exposed to the right antigen 3 Cells that are normally highly mitotic tissues subject to continual renewal by production of new cells divide at a high rate Spermatogonia that become sperm Epithelial cells o Lengths of cell cycles are variable particularly at different stages of development 30 minutes in very rapidly dividing cleaving embryo cells Not mammals which cleave very slowly Several months in slowly growing tissues like mammalian liver Rapidly growing adult cells typically divide every 12 36 hours o Transition points Two main transition points in the cell cycle 1 Initiation of DNA replication start checkpoint o At transition between G1 and S o Checks if environment is favorable if there is enough room 2 Initiation of mitosis G2 M checkpoint o At transition between G2 and M o Checks if all DNA is replicated and if environment is favorable Third checkpoint at anaphase before chromosomes separate metaphase to anaphase transition trigger anaphase and proceed to cytokinesis Checks to make sure all chromosomes are attached to the spindle The cell cycle control system triggers the essential process of the cycle such as DNA replication mitosis and cytokinesis The controller rotates clockwise and triggers these processes when it reaches specific checkpoints on the outer dial Information about the cycle events and signals from the environment can cause the control system to arrest the cycle at these checkpoints o A cytoplasmic factor can trigger passage through the transition points into Rao Johnson used a virus to fuse cells in different stages of the S or M cycle A Fuse G1 cells S cells the nucleus that was originally from the G1 cell enters the S phase o S Cells have replication signal s that stimulate the initiation of DNA synthesis in nucleus from G1 cell B Fuse G2 cells M cells the nucleus that was originally from the G2 cell undergoes premature chromosomal condensation in preparation for mitosis o M cells have replication signal s that stimulate mitosis in the nucleus from G2 cell Concluded that transitions of donated nuclei G1 S and G2 M were induced by the presence of some stimulatory agent in the cytoplasm of S and M cells o Cyclin dependent kinases and cyclins are the main cytoplasmic proteins that trigger passage through the transition points Entry into S or M is triggered by activation of a cytoplasmic factor a two subunit protein kinase in the case of entry into M this has been called a maturation promoting factor MPF Components of the protein kinase or MPF that controls progression through the cell cycle 1 Cyclin dependent kinase Cdk a catalytic subunit Phosphorylates serine threonine residues on proteins involved in mitosis or DNA synthesis so as to tigger their activity o Nuclear proteins histone H1 phosphorylation may help compact chromosomes o Nuclear lamins line the nuclear envelope phosphorylation leads to disassembly of nuclear envelope o Phosphorylated cytoplasmic proteins may be needed for dynamic changes in cytoskeleton organization characterizing shift from interphase to mitosis Cdk levels are constant throughout the cell cycle 2 Cyclin a regulatory subunit A family of proteins whose concentration rises and falls predictably during the cell cycle Regulates the activity of the catalytic subunit o When a cyclin is present in the cell it binds to the Cdk causing a change in conformation Cyclin binding causes a flexible loop of the kinase s polypeptide chain to move away from the active site allows kinase to phosphorylate its protein substrates Different cyclin genes are expressed at different stages of the cell cycle allows for fine tuning of kinase function The levels concentration of the cyclin increase and decrease The level increases just before the checkpoints where they will bind to Cdk to activate it Cyclin levels regulate MPF or Cdk activity o Low cyclin MPF activity low o High cyclin MPF high Slowly ramps up before mitosis constant o Role of multiple cyclins and Cdk s in the mammalian cell cycle Interaction between various members of the Cdk gene family and the cyclin gene family drive mammalian cells through the cell cycle Knockout of these cyclins and kinases result in a variety of growth and developmental deficiencies o Because of pathway redundancy more than one cyclin
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