Chapter 18-19 Cell-Cycle Control and Cell Death

Cell reproduce by duplicating their contents and dividing in

two, a process called the cell cycle
 Cell-Cycle Central Questions:

1. How do cells duplicate their contents?

2. How do they partition the duplicated contents and split in two?
3. How do they coordinate all the machinery that is required for
these two processes?
The cell cycle is divided into four phases
 The essential processes of the cell cycle, such as DNA
replication, mitosis, and cytokinesis, are triggered by a cell-
cycle control system
The cell-cycle control system can arrest the
cycle at various checkpoints
How do cells coordinate all the machinery that is required for the
cell cycle progression?
The cell-cycle control system depends on
cyclically activated protein kinases
Distinct Cdks associate with different cylins to trigger
different events of the cell cycle
 Cyclin-dependent protein kinases are regulated by the
accumulation and destruction of cyclins

The increase in M-cyclin concentration leads to the

formation of the active M-cyclin-Cdk complex (M-Cdk),
which drives entry into M phase.
 Cyclin-dependent protein kinases are regulated by the
accumulation and destruction of cyclins

M-cyclin concentration increases gradually throughout interphase,

but M-Cdk activity switches abruptly at the end of interphase. So,
what triggers this rapid activation of M-Cdk?
Ubiquitination of a cyclin marks the protein for destruction. Loss
of the cyclin leaves Cdk partner inactive
For M-Cdk to be active, the inhibitory phosphate must be removed
Activated M-Cdk indirectly activates more M-Cdk

This positive feedback

produces the sudden,
explosive increase in M-Cdk
activity that drives the cell
abruptly into M-phase
The cell-cycle control system uses various mechanisms to pause the cycle at
specific transition points
DNA damage
arrests the cell
cycle in G1
During every cell-cycle, DNA replication is initiated
at the right timeand no more than once per cycle.
Distinct Cdks associate with different cylins to trigger the
different events of the cell cycle
S-Cdk triggers DNA replication and ensures that DNA
replication is initiated only once per cell cycle
Cohesins tie together the two adjacent sister chromatids
in each replicated chromosome
Condensins help to coil the mitotic chromatids into smaller,
more compact structures that can be more easily segregated
during mitosis
Two transient cytoskeletal structures mediate M phase in
animal cells
At the beginning of anaphase, each pair of sister
chromotids separates
 The centrosome in an
interphase cell duplicates to
form the two poles of a
mitotic spindle
A bipolar mitotic spindle is formed
by the selective stabilization of
interacting microtubules
Kinetochores attach chromosomes to the mitotic spindle
Three classes of microtubules make up the mitotic spindle
Motor proteins and chromosomes can direct the assembly of a
functional bipolar spindle in the absence of centrosomes
The APC triggers the separation of sister chromatids by
promoting the destruction of cohesins
Two processes segregate daughter chromsomes at anaphase
The nuclear envelope breaks down and reforms during mitosis
Apotosis in the developing mouse paw sculpts the digits
Apotosis helps eliminate the tail during the
metamorphosis of a tadpole into a frog
Necrosis and apoptosis
Apoptosis is mediated by an intracellular proteolytic cascade
Apoptosis is regulated by members of the Bcl-2 family of
intracellular proteins
Each Cell is Programmed to Respond to Specific Combinations of
Extracellular Signal Molecules
Animal Cells Require Extracellular Signals to Divide, Grow and
Survive

1. Mitogens stimulate cell division, primarily by overcoming the

intracellular braking mechanisms that tend to block progression
through cell cycle
Rb (retinoblastoma)
protein binds to
particular gene
regulatory proteins,
preventing them from
stimulating the
transcriptions required
for cell proliferation
Animal Cells Require Extracellular Signals to Divide, Grow and
Survive

1. Mitogens stimulate cell division, primarily by overcoming the

intracellular braking mechanisms that tend to block progression
through cell cycle

2. Growth factors stimulate cell growth (an increase in cell mass)

by promoting the synthesis and inhibiting the degradation of
proteins and other macromolecules.
Extracellular growth factors
increase the synthesis and
decrease the degradation of
macromolecules
Animal Cells Require Extracellular Signals to Divide, Grow and Survive

1. Mitogens stimulate cell division, primarily by overcoming the intracellular

braking mechanisms that tend to block progression through cell cycle

2. Growth factors stimulate cell growth (an increase in cell mass) by

promoting the synthesis and inhibiting the degradation of proteins and other
macromolecules.

3. Survival factors promote cell survival by suppressing apoptosis.

Cell death helps match the number of developing nerve cells to the
number of target cells they contact
 Survival factors often
suppress apoptosis by
regulating Bcl-2 family
members

Figure 18-42 Essential Cell Biology ( Garland Science 2010)

Chapter 18 - Cell Cycle

Overall Objective: Understand how cells progress through the cell division cycle and how this progression is
regulated.

Specific Objectives:

1) Know the basic stages of the cell cycle.

2) Understand how cyclins and cyclin-dependent kinases regulate progression through the cell cycle.

3) Understand the basic movements of the chromosomes in interphase and mitosis and the cytoskeletal structures
needed for chromosome segregation and cell division.

Questions: 18-2; 18-3; 18-4; 18-5; 18-6; 18-7, 18-10, 18-12, 18-13, 18-15, 18-16, 18-17, 18-26, 18-30.