Download V. Lecture Section 5 A. Review of the mitotic cell cycle and cell death

V. Lecture Section 5
A. Review of the mitotic cell cycle and cell death (Chapter 17, 18)
1. Cell number is a combination of cell division and cell death
2. Prokaryotic cells divide by binary fission
a. Circular DNA is copied and separate to opposite poles
b. Cell separates into two daughter cells
3. Certain protists have mechanism intermediate between binary fission and mitosis
4. Eukaryotic cell cycle is divided into four phases
a. Gap 1: necessary to allow more time for growth after the previous cell division
and to prepare for DNA synthesis
b. Synthesis: DNA synthesis occurs
c. Gap 2: necessary to prepare for cell division
d. Cell Division: mitosis and cytokinesis
B. Regulation of cell number and quality during mitosis (Chapter 17, 18)
1. Review
a. Cell receives signal to: survive, grow and divide, differentiate, or die
b. If told to divide
1. Interphase: Gap 1, Synthesis, Gap 2
2. Mitotic cell division (or M phase): prophase, metaphase, anaphase,
telophase, and cytokinesis
2. Regulation
a. Four major checkpoints that regulate progression through cell cycle
1. G1/S checkpoint – to enter the cycle or not
2. S-checkpoint – to synthesize DNA or not
3. G2/M checkpoint – to divide the cell or not
4. M-checkpoint – to shift from metaphase to anaphase
b. Cell in G1 can either “go” or switch into nondividing state called G0 phase
1. Stop and Go regulation at the G1 checkpoint
c. Cyclins and Cyclin-dependent kinases control cell cycle checkpoints
1. Cychins are expressed and degraded; when present, the cell
moves forward
2. Cyclin-dependent kinases (Cdks) are always present and are
activated by the binding of their appropriate cyclin
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d. What does cyclin:cdk phosphorylate?
1. G1-cdk phosphorylates Rb protein, in turn, loses inhibition of
E2F
2. M-cdk phosphorylates histones , lamins , and myosin
e. What happens when something goes wrong?
1. Internal activation of apoptosis = Intrinsic apoptotic pathway
2. External activation of apopotosis = Extrinsic apoptotic pathway
3. Activation of Caspase Cascade
4. Characteristics include cessation of DNA repair mechanisms,
cell shrinkage, nuclear membrane blebbing, DNA fragmentation,
and death
C. Regulation of cell type during cell division (Chapter 17, 22)
1. Review
a. Symmetric vs. asymmetric cell division
1. Commonly both daughter cells are just like parent cell
2. In many differentiation events both daughters are not like parent
3. In specialized stem cell differentiations one daughter cell is like the
parent cell, while the other is different
b. Stem cell and embryonic cell divisions
1. Cells that divide in the adult
2. Embryonic cell divisions and differentiations
3. Cancer: dedifferentiation or stem cell mutation?
2. Regulation
a. Control in the cytosol
1. G2 phase development across the cleavage plane
2. The specialized case of embryonic cleavage
b. Control in the nucleus
1. Gene availability, euchromatin and heterochromatin structure
2. Transcription factors, SNuRPs and other regulators
D. Wound Healing: The cellular response to disruptions in architecture
1. Clotting, scarring and re-establishment of function in complex tissues
2. The four overlapping stages of wound repair
a. Hemostasis stops the loss of blood and sets the stage for repair
1. Spilled blood and the fibrous clot
2. Platelet degranulation activates much of the ensuing response
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b. Inflammation disinfects and accelerates the response
1. Mast cells supply most of the visual aspects of healing.
2. Circulating and local monocytes are activated to become macrophages.
3. Circulating neutrophils arrive first to clean out bacteria.
c. Proliferation re-establishes most or all of their pre-wound functions
1. Reconnection of the dermal connective tissue
2. Integrity of the epidermal layers
3. Re-establishment of blood flow
d. Maturation of the scar maximizes restored function.
1. Contracture minimized the final scar area
2. Fibroblasts and macrophages remodel collagen for a year +.
3. Two major points of error are common.
a. Failure to heal usually results from extended Inflammatory Stage.
1. Non-healing wounds are often treated with anti-inflammatories.
b. Fibrosis results from excessive formation of scar matrix tissues.
1. Hypertrophic scars don’t have fibroblast contracture.
2. Keloid scars are associated with excessive TGF- activity.
a. Too much made and fibroblasts with too many receptors.
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