KEY CONCEPTS 12.1 Most cell division results in genetically identical daughter cells 12.2 The mitotic phase alternates with interphase in the cell cycle 12.3 The eukaryotic cell cycle is regulated by a molecular control system

1. Chapter 11 Addendum
Apoptosis—programmed cell death; organized
series of events to recapture biomolecules in an
ordered fashion and utilize metabolites from the
cells that are dying; DNA fragmented, cell
shrinks into blebs that can then be digested by
phagocytic cells
Vs.
Necrosis—decaying tissue from wound,
infection, cell contents leak out of membrane
systems and enzymes can damage surrounding
tissue

2. Apoptosis pathways in nematodes and
mammals
Discovered in
worms, analogs
in mammals
Pink=major proteases
involved in scavenging

3. Apoptosis controls
• External signals involved in development e.g.
removing webbing from digits. Works as signal
transduction
• Internal signals such as excessive DNA damage
and increased mis-folded proteins in ER to
avoid necrotic tissue damage

4. Disruption of normal brain development by
blocking apoptosis
Extra neurons & webbed digits

5. Chapter 12
The Cell Cycle

6. Reproduction
100 µm
Tissue renewalGrowth and development
20 µm200 µm
The Key Roles of Cell Division
•Reproduction
•Repair e.g. wound healing
•Growth
•Replacement e.g. skin

7. Animal mitosis video live

8. Cell division results in genetically
identical daughter cells
• Cells duplicate their genetic material before they
divide, ensuring that each daughter cell receives an
exact copy of the genetic material, DNA
• A dividing cell duplicates its DNA, allocates the two
copies to opposite ends of the cell, and only then
splits into daughter cells
• A cell’s endowment of DNA (its genetic
information) is called its genome
• DNA molecules in a cell are packaged into
chromosomes

9. • Every eukaryotic species has a characteristic
number of chromosomes in each cell nucleus
• Somatic (nonreproductive) cells have two sets
of chromosomes = 2n (diploid)
• Germ cells (reproductive cells: sperm and eggs)
have half as many chromosomes as somatic
cells = 1n (haploid)
• Eukaryotic chromosomes consist of chromatin,
a complex of DNA and protein that condenses
during cell division (about 50/50)

10. Fig. 4.6

11. Distribution of Chromosomes During
Cell Division
• In preparation for cell division, DNA is replicated
and the chromosomes condense
• Each duplicated chromosome has two sister
chromatids, which separate during cell division
• The centromere is the narrow “waist” of the
duplicated chromosome, where the two
chromatids are most closely attached

12. Figure 12.5-3
Chromosomes
Centromere
Chromosome
arm
Chromosomal
DNA molecules
1
Chromosome
duplication
Sister
chromatids
2
3
Separation of
sister chromatids

13. Fig. 4.5

14. • Eukaryotic cell division consists of:
– Mitosis, the division of the nucleus
– Cytokinesis, the division of the cytoplasm
• Gametes are produced by a variation of cell
division called meiosis
• Meiosis yields nonidentical daughter cells that
have only one set of chromosomes, half as
many as the parent cell

15. LE 12-5
G1
G2
S
(DNA synthesis)
INTERPHASE
Cytokinesis
MITOTIC(M) PHASE
M
itosis
Phases of the Cell Cycle

16. • Mitosis is conventionally divided into five phases:
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
• Cytokinesis is well underway by late telophase

17. Fig. 4.8

18. The Mitotic Spindle: A Closer Look
• The mitotic spindle is an apparatus of
microtubules that controls chromosome
movement during mitosis
• Assembly of spindle microtubules begins in the
centrosome, the microtubule organizing center
• The centrosome replicates in interphase,
forming two centrosomes that migrate to
opposite ends of the cell, as spindle
microtubules grow out from them
• An aster (a radial array of short microtubules)
extends from each centrosome

19. Figure 12.8
Sister
chromatids
Aster
Centrosome
Metaphase
plate
(imaginary)
Kineto-
chores
Kinetochore
microtubules
Microtubules
Overlapping
nonkinetochore
microtubules
Chromosomes
Centrosome
1 µm 0.5 µm
The spindle includes the
centrosomes, the spindle
microtubules, and the asters
MT: aster, kinetochore, polar

20. Chromosome
movement
Microtubule Motor
protein
Chromosome
Kinetochore
Tubulin
subunits
•In anaphase, sister chromatids separate and move along
the kinetochore microtubules toward opposite ends of the
cell
•In anaphase the cohesins are cleaved by an enzyme
called separase
•The microtubules shorten by depolymerizing at their
kinetochore ends

21. • Nonkinetochore (or polar) microtubules from
opposite poles overlap and push against each
other, elongating the cell
• In telophase, genetically identical daughter
nuclei form at opposite ends of the cell

22. Figure 12.10
(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)
Cleavage furrow
Contractile ring of
microfilaments
Daughter cells
100 µm
1 µm
Daughter cells
New cell wallCell plate
Wall of parent cellVesicles
forming
cell plate
Cytokinesis: division of cytoplasm;
begins in anaphase or telophase

23. Figure 12.11
Nucleus
10µm
Nucleolus
Chromosomes
condensing Chromosomes
PrometaphaseProphase
Cell plate
1 2
3 4 5Metaphase Anaphase Telophase

24. Binary Fission
• Prokaryotes (bacteria and archaea) reproduce
by a type of cell division called binary fission
• In binary fission, the chromosome replicates
(beginning at the origin of replication), and the
two daughter chromosomes actively move
apart

25. Figure 12.12-4
Chromosome
replication
begins.
Two copies
of origin
E. coli cell
Origin of
replication
Cell wall
Plasma
membrane
Bacterial
chromosome1
2 Origin OriginOne copy of the
origin is now at
each end of the
cell.
3
Two daughter
cells result.
4
Replication
finishes.

26. The Evolution of Mitosis
• Since prokaryotes evolved before eukaryotes,
mitosis probably evolved from binary fission
• Certain protists exhibit types of cell division that
seem intermediate between binary fission and
mitosis

27. Figure 12.13
Bacterial
chromosome
(a) Bacteria
Chromosomes
Microtubules
Intact nuclear
envelope
(b) Dinoflagellates (d) Most eukaryotes
Fragments
of nuclear
envelope
Kinetochore
microtubule
Kinetochore
microtubule
(c) Diatoms and some yeasts
Intact
nuclear
envelope

28. 1. Which of the following best
describes the kinetochore?
a. a structure composed of several proteins that
associate with the centromere region of a
chromosome and that can bind to spindle
microtubules
b. the centromere region of a metaphase chromosome
at which the DNA can bind with spindle proteins
c. the array of vesicles that will form between two
dividing nuclei and give rise to the metaphase plate
d. the ring of actin microfilaments that will cause the
appearance of the cleavage furrow
e. the core of proteins that forms the cell plate in a
dividing plant cell

29. 1. Which of the following best
describes the kinetochore?
a. a structure composed of several proteins that
associate with the centromere region of a
chromosome and that can bind to spindle
microtubules
b. the centromere region of a metaphase chromosome
at which the DNA can bind with spindle proteins
c. the array of vesicles that will form between two
dividing nuclei and give rise to the metaphase plate
d. the ring of actin microfilaments that will cause the
appearance of the cleavage furrow
e. the core of proteins that forms the cell plate in a
dividing plant cell

30. The eukaryotic cell cycle is regulated by
a molecular control system
• The frequency of cell division varies with the
type of cell
• These cell cycle differences result from
regulation at the molecular level
• The cell cycle appears to be driven by specific
chemical signals present in the cytoplasm
• Some evidence for this hypothesis comes from
experiments in which cultured mammalian cells
at different phases of the cell cycle were fused
to form a single cell with two nuclei

31. Figure 12.14
Experiment 1 Experiment 2Experiment
Results
Conclusion
S
S S
G1
G1M
M M
G1 nucleus
immediately entered
S phase and DNA
was synthesized.
G1 nucleus began
mitosis without
chromosome
duplication.
Molecules present in the cytoplasm control
the progression to S and M phases.

32. LE 12-14
G1 checkpoint
G1
S
M
M checkpoint
G2 checkpoint
G2
Control
system
The clock has specific
checkpoints where the cell
cycle stops until a go-ahead
signal is received

33. LE 12-15
G1
G1 checkpoint
G1
G0
If a cell receives a go-ahead
signal at the G1 checkpoint,
the cell continues on in the
cell cycle.
If a cell does not receive a
go-ahead signal at the G1
checkpoint, the cell exits the
cell cycle and goes into G0, a
nondividing state.
For many cells, the G1
checkpoint seems to be
the most important one

34. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
The Cell Cycle Clock: Cyclins and
Cyclin-Dependent Kinases
• Two types of regulatory proteins are involved in
cell cycle control: cyclins and cyclin-dependent
kinases (Cdks)
• The activity of cyclins and Cdks fluctuates
during the cell cycle
• MPF (maturation-promoting factor) is a cyclin-
Cdk complex that triggers a cell’s passage past
the G2 checkpoint into the M phase

35. Figure 12.16
MPF
activity
(a) Fluctuation of MPF activity and cyclin
concentration during the cell cycle (b) Molecular mechanisms that help regulate
the cell cycle
Time
Degraded
cyclin
Cdk
Cyclin is
degraded
MPF Cyclin
Cdk
G2
checkpoint
Cyclin
concentration
M M M G1G2G2G1 G1S S
G
1
S
G 2
M

36. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
Stop and Go Signs: Internal and External Signals at
the Checkpoints
• An example of an internal signal is that
kinetochores not attached to spindle
microtubules send a molecular signal that
delays anaphase
• Some external signals are growth factors,
proteins released by certain cells that stimulate
other cells to divide
• For example, platelet-derived growth factor
(PDGF) stimulates the division of human
fibroblast cells in culture

37. Copyright © 2005 Pearson Education, Inc. publishing as Benjamin Cummings
PowerPoint Lectures for
Biology, Seventh Edition
Neil Campbell and Jane Reece
Lectures by Chris Romero
Figure 12.18-4
Scalpels
1
Petri
dish
A sample of
human connective
tissue is cut
up into small
pieces.
2
Enzymes digest
the extracellular
matrix, resulting
in a suspension of
free fibroblasts.
3
Cells are transferred
to culture vessels.
4 PDGF is added
to half the
vessels.
Without PDGF With PDGF Cultured fibroblasts (SEM)
10µm

38. • Another example of external signals is density-
dependent inhibition, in which crowded cells
stop dividing
• Most animal cells also exhibit anchorage
dependence, in which they must be attached to
a substratum in order to divide
• Cancer cells do NOT have either

39. Figure 12.19
Anchorage dependence: cells
require a surface for division
Density-dependent inhibition:
cells form a single layer
Density-dependent inhibition:
cells divide to fill a gap and
then stop
(a) Normal mammalian cells (b) Cancer cells
20 µm 20 µm

40. Loss of Cell Cycle Controls in Cancer Cells
• Cancer cells do not respond normally to the
body’s control mechanisms
• Cancer cells form tumors, masses of abnormal
cells within otherwise normal tissue
• If abnormal cells remain at the original site, the
lump is called a benign tumor
• Malignant tumors invade surrounding tissues
and can metastasize, exporting cancer cells to
other parts of the body, where they may form
secondary tumors

41. • Cancer cells may not need growth factors to
grow and divide
– They may make their own growth factor
– They may convey a growth factor’s signal without
the presence of the growth factor
– They may have an abnormal cell cycle control
system

42. Figure 12.20
Tumor
Glandular
tissue
A tumor grows
from a single
cancer cell.
1 2 3
Cancer cells invade
neighboring tissue. Cancer cells spread
through lymph and
blood vessels to other
parts of the body.
4
A small percentage
of cancer cells may
metastasize to
another part of the
body.
Cancer
cell
Blood
vessel
Lymph
vessel
Breast cancer cell
(colorized SEM)
Metastatic
tumor
5µm

43. 2. Of the events of a typical cell division listed below,
which is most likely to occur THIRD in an animal cell
that is going through mitosis?
a. Kinetochore proteins associated with the
centromeres bind with associated microtubules.
b. Segregation of complete genomic sets of
chromosomes occurs.
c. The nuclear envelope membranes are converted
from flat bilayers into many spherical vesicles.
d. The number of chromosomes in the cell doubles as
double-chromatid chromosomes are split into pairs
of single-chromatid chromosomes.
e. Vesicles fuse to one another to form new nuclear
envelope membranes.

44. 2. Of the events of a typical cell division listed below,
which is most likely to occur THIRD in an animal cell
that is going through mitosis?
a. Kinetochore proteins associated with the centromeres bind
with associated microtubules. prometaphase
b. Segregation of complete genomic sets of chromosomes
occurs. Anaphase—simultaneous with d
c. The nuclear envelope membranes are converted from flat
bilayers into many spherical vesicles.
Prophase/Prometaphase
d. The number of chromosomes in the cell doubles as double-
chromatid chromosomes are split into pairs
of single-chromatid chromosomes. Anaphase
e. Vesicles fuse to one another to form new nuclear envelope
membranes. telophase