7.lecture apoptosis and cell cycle

8/3/2019 7.Lecture Apoptosis and Cell Cycle

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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)

7.lecture apoptosis and cell cycle

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