Cell Differentiation and Death

The most basic function of the cell cycle is to —- and then —

duplicate the DNA

segregate the copies into two genetically identical daughter cells.

Chromosome duplication occurs during — phase

S

(S for DNA synthesis)

After S phase, chromosome segregation and cell division occur in —

M phase (M for mitosis)

M phase comprises two major events:

mitosis and cytokinesis

Most cells require much more time to grow and double their mass of proteins and organelles than they require to duplicate their chromosomes and divide. Because of this, the cell cycle has —

gap phases

G1 phase is

between M phase and S phase

G2 phase between —

S phase and M phase

—,—,— together are called interphase

G1, S, and G2

Cell growth occurs throughout the cell cycle, except during—

mitosis.

If extracellular conditions are unfavorable, for example, cells delay progress through G1 and may even enter a specialized resting state known as —

G0 (G zero) (senescence)

state the phases clearly

constant “ON” signal wouldn’t work. The cell needs:

• Low kinase activity at some times

• High kinase activity at others

Cyclin-Dependent Kinases (Cdks) are —

protein kinases

A lone Cdk is inactive, but the binding of a — activates it

cyclin

okay at first I just thought the CDK aciavtes the cyclin, but why is that wrong?

it’s the opposite

it’s actually the cyclin that activates the CDK

the CDK is then active to act as a kinase and go phosphorylate a bunch of unnamed players

so why do we need so many different cyclins and kinases?

well there is one for each phase and

• The cyclin doesn’t just activate the Cdk

• It also directs the kinase to specific substrate target proteins

• Each cyclin–Cdk complex phosphorylates a distinct set of targets

• This triggers stage-specific event

Cdk Inhibitor Proteins can be good as —

an extra layer of control/regulation

DNA damage is an input that can immeditaly stop the cell cycle, it can

1. do dna repair

2. do apoptosis

3. —

inactivate CDKs directly to pause the cell cycle

How does one cell give rise to many different, stable cell identities?

Cell identity is defined by gene expression, not gene content

Since DNA is (mostly) the same in all cells:

• Differences between cells arise from which genes are ON or OFF

• Gene expression patterns determine:

  • Structure

  • Function

  • Future potential

—: the major developemnt restriction event

Gastrulation

Development does not jump directly from pluripotent to fully specialized.

Instead:

• Cells pass through a series of —

• Each step:

  • Narrows potential

  • Stabilizes identity

• intermediate states

The genome is the same in a muscle cell as in a skin cell, but different genes are active because

these cells express different transcription regulators that bind to gene regulatory elements

f cells died randomly:

• They would burst

• Spill contents

• Damage neighbors

• Trigger inflammation

This would be catastrophic in tightly packed tissues.

so we developped:

controlled, non-damaging way for cells to die 9programmed cell death: apoptosis)

some reasons we need apoptosis

• make fingers/structures

• quality control: get rid of dysfunctional cells

The apoptosis cascade is driven by:

Caspases are:

• — (protein-cutting enzymes)

• Proteases

Two functional classes of caspases

• initiator

• excuetcuioner

Two ways to trigger apoptosis

, death signals can come from:

• jj

• —

• Outside the cell

• Inside the cell

Thus apoptosis has two pathways:

extrinsic (death signal from outside) aka death receptor pathway

intrinsic (death signalin from within cell)

Some cells must be killed on command by the Immune system

Killer lymphocyte s

• Expresses — on its surface

• Fas ligand

the target cell (to die)

• Expresses the — on its surface

• Fas death receptor

when Fas binds to death receptor, then what?

death domains ( and adaptor protein called FADD) are actiavted inside the cell

then what happens?

FADD recruits initiator caspase-8 and they form the DISC (Death-Inducing Signaling Complex)

then what?

Caspase-8 activates executioner caspases

those caspases will trigger apoptosis

one part of apoptosis is destroying dna so that its not reused,

DNA is not destroyed randomly

DNA is cut at specific locations

where do the cuts happen?

Between nucleosomes, in the linker regions

this produces fragments of DNA that are ~180 bp

a key organelle involved in the intrinsic apoptosis pathway

mitochondria

the mitcohdonria releases:

cytochrome c

cytochrome c activates

Apaf1

Apaf1 causes

formation of the apoptosome

formation of the apoptosome causes

recruitment of caspcase 9 (excecuioner)

The intrinsic pathway is tightly regulated by —

Bcl2 family proteins.

what are the 3 groups in the Bcl2 family proteins.

• anti-apoptotic

• pro-apoptotic

• BH3 only proteins

Anti-apoptotic

• Bcl2,

• Block—-

• mitochondrial protein release (cytochrome c)

Pro-apoptotic effectors

• Bax, Bak

• Allow —

• mitochondrial protein release (cytochrome c)

BH3-only proteins

• Inhibit —

• anti-apoptotic proteins

• (so they tip the scaled towards apoptosis happening)

If survival factors disappear → —

apoptosis begins.

default is NOT survival

Some survival factors:

• Activate —

• Increase synthesis of —

• transcription

• Bcl2,