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The cell cycle &Cell death
M. Cengiz YAKICIER
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Egg cell
Sperm cell
Fertilized egg
with DNA from
both parents
Embyros cellswith copies ofinherited DNA
Offspringwith traits
inherited from
both parents
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More than 200 cell types identified in human bodyArranged into tissues - 4 basic tissue types
epithelia connective tissue muscle
nervous tissue
rod cells - photoreceptor cells
hair cell - sound receptor
germ cell - sperm
red blood cells
Specialised cell types:
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Binary Fission
Prokaryotes (bacteria and archaea)
reproduce by a type of cell division calledbinary fission
In binary fission, the chromosome replicates
(beginning at the origin of replication), and
the two daughter chromosomes actively
move apart
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Origin of
replication
Cell wall
Plasma
membrane
Bacterial
chromosome
E. colicell
Two copies
of origin
Chromosomereplication begins.
Soon thereafter,
one copy of the origin
moves rapidly toward
the other end of the cell.
Replication continues.One copy of the origin
is now at each end of
the cell.
Origin Origin
Replication finishes.
The plasma membrane
grows inward, and
new cell wall is
deposited.
Two daughter
cells result.
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The Evolution of Mitosis Since prokaryotes evolved before
eukaryotes, mitosis probably evolved from
binary fission
Certain protists exhibit types of cell divisionthat seem intermediate between binary
fission and mitosis
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LE 12-12Bacterial
chromosome
Chromosomes
Microtubules
Prokaryotes
Dinoflagellates
Intact nuclear
envelope
Kinetochore
microtubules
Kinetochore
microtubules
Intact nuclear
envelope
Diatoms
Centrosome
Most eukaryotes
Fragments of
nuclear envelope
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The cell cycle: cells duplicate their
contents and divide
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The cell cycle may be divided into 4
phases
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The cell cycle triggers essential
processes (DNA replication, mitosis)
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Progression of the cell cycle is regulated by
feedback from intracellular events
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Cyclin-dependent protein kinases drive
progression through the cell cycle
Cyclin-dependent kinases
(Cdks) are inactive unless
bound to cyclins
Active complex
phosphorylates downstream
targets
Cyclin helps to direct Cdks to
the target proteins
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Cellular levels of (mitotic) M-cyclin rises
and falls during the cell cycle
M-cyclin levels are low during interphase but graduallyincreases to a peak level during mitosis
M-cdk activity is, likewise, low in interphase butincreases in mitosis
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The abundance of cyclins (and the activity of
Cdks) is regulated by protein degradation
M-cyclin becomes covalently modified by addition of multiple copies of
ubiquitin at the end of mitosis Ubiqutination is mediated by the anaphase promoting complex (APC)
Ubiquitination marks cyclins for destruction by large proteolytic
machines called proteasome
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Cdks are also regulated by cycles of
phosphorylation and dephosphorylation
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Cdk activates itself indirectly via a
positive feedback loop
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Distinct cyclins partner with distinct Cdks to
trigger different events of the cell cycle
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S-Cdk triggers DNA replication - its destruction
ensures this happens once per cell cycle
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Checkpoints ensure the cell cycle
proceeds without errors
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Checkpoint: DNA damage arrests the cell
cycle in G1
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Checkpoint: spindle assembly
Mitosis must not complete unless all thechromosomes are attached to the mitoticspindle
Mitotic checkpoint delays metaphase toanaphase transition until all chromosomesare attached
Prolonged activation of the checkpoint -->celldeath
Mechanism of many anti-cancer drugs
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Cells can withdraw from the cell cycle and
dismantle the regulatory machinery
G0 is a quiescent state
Cdks and cyclins disappear
Some cells enter G0 temporarily anddivide infrequenty (I.e. hepatocytes)
Other differentiated cell types (neurons)spend their life in G0
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Apoptosis: the necessity for cell death in
multicellular organisms
Embryonic morphogenesis
Killing by immune effector cells
Wiring of the developing nervous system
Regulation of cell viability by hormonesand growth factors (most cells die if theyfail to receive survival signals from othercells)
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Developmentally-regulated apoptosis
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Apoptosis vs. necrosis
Necrotic cell Apoptotic cells
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Necrosis
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Apoptosis
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QuickTime and adecompressor
are needed to see this picture.
Apoptosis occurs very quickly and
precisely
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Apoptotic cells are phagocytosed by
macrophages
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Caspases are specialized proteases that
mediate apoptosis
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Apoptosis is mediated by an intracellular
proteolytic cascade
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Cell-surface death receptors regulate the
extrinsic pathway of apoptosis
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The intrinsic pathway of apoptosis
depends on mitochondria
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The Bcl-2 family of proteins regulate the
intrinsic pathway of apoptosis
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QuickTime and aH.264 decompressor
are needed to see this picture.
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Animal cells require extracellular signals to
divide, grow, and survive
Mitogens - stimulate cell division by overcoming cell
cycle brake that leads to G0
Growth factors - stimulate growth (increased cell
size) by promoting synthesis and inhibiting
degradition of macromolecules
Survival factors - suppress apoptosis
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Mitogens stimulate proliferation by
inhibiting the Rb protein
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Growth factors increase synthesis &
decrease degradation of macromolecules
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Survival factors mediate essential cell
death during formation of the nervous
system
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Survival factors suppress apoptosis by
regulating Bcl-2 proteins
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Malfunction of apoptosis leads to disease
Cancer (TNF produced by
macrophages activates extrinsic
pathway)
Neurodegenerative diseases
AIDS (HIV deactivates Bcl-2)
Ischemic stroke
Autoimmune disease (lupus)
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