1. Outline: Mitosis and the Cell Cycle
Why we need cell division
Stages of the cell cycle
How bacteria are different
Regulating the cell cycle – how does a cell know when to go to the next stage?
Cancer – what happens when the cell cycle is unregulated
Figure 12.2 The functions of cell division

2. Cell division is important for:
Fig. 12-2
Cell division is important for:
100 µm
200 µm
20 µm
(a) Reproduction
(b) Growth and
development
(c) Tissue renewal
Figure 12.2 The functions of cell division

3. Cell division results in genetically identical daughter cells
Most cell division (mitosis) results in daughter cells with identical genetic information, DNA
A special type of division (meiosis) produces nonidentical daughter cells (gametes, or sperm and egg cells). These cells have half as much DNA as cells made by mitosis.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

4. Overview: Cell Division
2 ways to divide the cell’s DNA: mitosis and meiosis
Mitosis
Meiosis
Makes new somatic (body) cells
Makes reproductive cells (eggs and sperm)
Purpose: Growth, development, repair
Purpose: Reproduction
New daughter cells have the same number of chromosomes as the parent cell
New daughter cells have half as many chromosomes as the parent cell
“My toes are made by mitosis, my ova are made by meiosis.”
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5. Organization of the Genetic Material
All the DNA in a cell constitutes the cell’s genome
A genome can consist of a single DNA molecule (common in prokaryotic cells) or a number of DNA molecules (common in eukaryotic cells)
DNA molecules in a cell are packaged into chromosomes, which are DNA molecules wrapped around proteins called histones.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

6. Fig. 12-3
Figure 12.3 Eukaryotic chromosomes
20 µm

7. Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus
Somatic cells (nonreproductive cells) have two sets of chromosomes (1 from mom, 1 from dad)
Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells
Eukaryotic chromosomes are made condensed chromatin, a material made of DNA and protein
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

8. Human Gamete Cell Chromosomes Human Somatic Cell Chromosomes
Each chromosome is by itself – doesn’t have a homologous chromosome
Human Somatic Cell Chromosomes
Each chromosome is part of a pair of 2 homologous chromosomes

9. Distribution of Chromosomes During Eukaryotic Cell Division
In preparation for cell division, DNA is replicated and the chromosomes condense
Each duplicated chromosome has two identical 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

10. Fig. 12-UN3

11. 0.5 µm Chromosomes DNA molecules Chromo- some arm Chromosome
Fig. 12-4
0.5 µm
Chromosomes
DNA molecules
Chromo-
some arm
Chromosome
duplication
(including DNA
synthesis)
Centromere
Sister
chromatids
Figure 12.4 Chromosome duplication and distribution during cell division
Separation of
sister chromatids
Centromere
Sister chromatids

12. 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

13. Outline: Mitosis and the Cell Cycle
Why we need cell division
Stages of the cell cycle
How bacteria are different
Regulating the cell cycle – how does a cell know when to go to the next stage?
Cancer – what happens when the cell cycle is unregulated
Figure 12.2 The functions of cell division

14. Phases of the Cell Cycle
The cell cycle consists of
Mitotic (M) phase (mitosis and cytokinesis)
Mitosis has 5 subphases
Interphase (cell growth and copying of chromosomes in preparation for cell division)
Interphase has 3 subphases
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15. Interphase (about 90% of the cell cycle) can be divided into subphases:
G1 phase (“first gap”)
S phase (“synthesis”)
G2 phase (“second gap”)
The cell grows during all three phases, but chromosomes are duplicated only during the S phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16. G1 + S + G2 = Interphase M phase = Mitosis
Fig. 12-5
INTERPHASE S
(DNA synthesis) G1
Cytokinesis G2
Mitosis
Figure 12.5 The cell cycle
MITOTIC
(M) PHASE
G1 + S + G2 = Interphase M phase = Mitosis

17. Mitosis is conventionally divided into five phases:
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis is well underway by late telophase
For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files.
BioFlix: Mitosis
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

18. G1 S Cytokinesis Mitosis G2 MITOTIC (M) PHASE Prophase Telophase and
Fig. 12-UN1
INTERPHASE G1 S
Cytokinesis
Mitosis G2
MITOTIC (M) PHASE
Prophase
Telophase and
Cytokinesis
Prometaphase
Anaphase
Metaphase

19. G2 of Interphase Prophase Prometaphase
Fig. 12-6a
Figure 12.6 The mitotic division of an animal cell
G2 of Interphase
Prophase
Prometaphase

20. Chromosome, consisting of two sister chromatids
Fig. 12-6b
G2 of Interphase
Prophase
Prometaphase
Centrosomes
(with centriole
pairs)
Chromatin
(duplicated)
Early mitotic
spindle
Aster
Centromere
Fragments
of nuclear
envelope
Nonkinetochore
microtubules
Figure 12.6 The mitotic division of an animal cell
Nucleolus
Nuclear
envelope
Plasma
membrane
Chromosome, consisting
of two sister chromatids
Kinetochore
Kinetochore
microtubule

21. The Mitotic Spindle: A Closer Look
The mitotic spindle is an apparatus of microtubules that controls chromosome movement during mitosis
During prophase, assembly of spindle microtubules begins in the centrosome, the microtubule organizing center
The centrosome replicates, forming two centrosomes that migrate to opposite ends of the cell, as spindle microtubules grow out from them
For the Cell Biology Video Spindle Formation During Mitosis, go to Animation and Video Files.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

22. An aster (a radial array of short microtubules) extends from each centrosome
The spindle includes the centrosomes, the spindle microtubules, and the asters
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23. During prometaphase, some spindle microtubules attach to the kinetochores (parts of the centromere that attach to the spindle fibers) of chromosomes and begin to move the chromosomes
At metaphase, the chromosomes are all lined up at the metaphase plate, the midway point between the spindle’s two poles
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

24. Fig. 12-7
Aster
Centrosome
Sister
chromatids
Microtubules
Chromosomes
Metaphase
plate
Kineto-
chores
Centrosome
Figure 12.7 The mitotic spindle at metaphase
1 µm
Overlapping
nonkinetochore
microtubules
Kinetochore
microtubules
0.5 µm

25. Fig. 12-UN4

26. Telophase and Cytokinesis
Fig. 12-6c
Figure 12.6 The mitotic division of an animal cell
Metaphase
Anaphase
Telophase and Cytokinesis

27. Telophase and Cytokinesis
Fig. 12-6d
Metaphase
Anaphase
Telophase and Cytokinesis
Metaphase
plate
Cleavage
furrow
Nucleolus
forming
Figure 12.6 The mitotic division of an animal cell
Daughter
chromosomes
Nuclear
envelope
forming
Spindle
Centrosome at
one spindle pole

28. The microtubules shorten by depolymerizing at their kinetochore ends
In anaphase, sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell
The microtubules shorten by depolymerizing at their kinetochore ends
For the Cell Biology Video Microtubules in Anaphase, go to Animation and Video Files.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

29. Nonkinetochore 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
For the Cell Biology Video Microtubules in Cell Division, go to Animation and Video Files.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

30. Cytokinesis: A Closer Look
In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
In plant cells, a cell plate forms during cytokinesis
Animation: Cytokinesis
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

31. (a) Cleavage of an animal cell (SEM)
Fig. 12-9a
100 µm
Cleavage furrow
Figure 12.9a Cytokinesis in animal and plant cells
Contractile ring of
microfilaments
Daughter cells
(a) Cleavage of an animal cell (SEM)

32. (b) Cell plate formation in a plant cell (TEM)
Fig. 12-9b
Vesicles
forming
cell plate
Wall of
parent cell
1 µm
Cell plate
New cell wall
Figure 12.9b Cytokinesis in animal and plant cells
Daughter cells
(b) Cell plate formation in a plant cell (TEM)

33. Nucleus 1 Prophase Chromatin condensing Nucleolus Fig. 12-10a
Figure Mitosis in a plant cell 1
Prophase

34. Chromosomes 2 Prometaphase Fig. 12-10b
Figure Mitosis in a plant cell 2
Prometaphase

35. Fig c
Figure Mitosis in a plant cell 3
Metaphase

36. Fig d
Figure Mitosis in a plant cell 4
Anaphase

37. 10 µm Cell plate 5 Telophase Fig. 12-10e
Figure Mitosis in a plant cell 5
Telophase

38. Fig. 12-UN5

39. Outline: Mitosis and the Cell Cycle
Why we need cell division
Stages of the cell cycle
How bacteria are different
Regulating the cell cycle – how does a cell know when to go to the next stage?
Cancer – what happens when the cell cycle is unregulated
Figure 12.2 The functions of cell division

40. 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

41. Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Bacterial
chromosome
Two copies
of origin
Figure Bacterial cell division by binary fission

42. Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Bacterial
chromosome
Two copies
of origin
Origin
Origin
Figure Bacterial cell division by binary fission

43. Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Bacterial
chromosome
Two copies
of origin
Origin
Origin
Figure Bacterial cell division by binary fission

44. Cell wall Origin of replication Plasma membrane E. coli cell Bacterial
Fig
Cell wall
Origin of
replication
Plasma
membrane
E. coli cell
Bacterial
chromosome
Two copies
of origin
Origin
Origin
Figure Bacterial cell division by binary fission

45. 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

46. Fig
Bacterial
chromosome
(a) Bacteria
Chromosomes
Microtubules
Intact nuclear
envelope
(b) Dinoflagellates
Kinetochore
microtubule
Intact nuclear
envelope
Figure A hypothetical sequence for the evolution of mitosis
(c) Diatoms and yeasts
Kinetochore
microtubule
Fragments of
nuclear envelope
(d) Most eukaryotes

47. Outline: Mitosis and the Cell Cycle
Why we need cell division
Stages of the cell cycle
How bacteria are different
Regulating the cell cycle – how does a cell know when to go to the next stage?
Cancer – what happens when the cell cycle is unregulated
Figure 12.2 The functions of cell division

48. The eukaryotic cell cycle is regulated by a molecular control system
The frequency of cell division varies with the type of cell – some cells stop dividing altogether
These cell cycle differences result from regulation due to signaling molecules
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

49. Evidence for Cytoplasmic Signals
The cell cycle appears to be driven by specific chemical signals present in the cytoplasm
We know this because if you put cytoplasm from one cell into a different cell, it can move that cell ahead in the cell cycle
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

50. EXPERIMENT RESULTS Experiment 1 Experiment 2 S G1 M G1 S S M M
Fig
EXPERIMENT
Experiment 1
Experiment 2 S G1 M G1
RESULTS S S M M
When a cell in the
S phase was fused
with a cell in G1, the G1
nucleus immediately
entered the S
phase—DNA was
synthesized.
When a cell in the
M phase was fused with
a cell in G1, the G1
nucleus immediately
began mitosis—a
spindle formed and
chromatin condensed,
even though the
chromosome had not
been duplicated.
Figure Do molecular signals in the cytoplasm regulate the cell cycle?

51. The Cell Cycle Control System
The events of the cell cycle are directed by a cell cycle control system, which is similar to a clock
The cell cycle control system is regulated by internal and external controls
The clock has specific checkpoints where the cell cycle stops until a go-ahead signal (one of those molecules in the cytoplasm) is received
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

52. G1 checkpoint Control system S G1 G2 M M checkpoint G2 checkpoint
Fig
G1 checkpoint
Control
system S G1 G2 M
Figure Mechanical analogy for the cell cycle control system
M checkpoint
G2 checkpoint

53. For many cells, the G1 checkpoint seems to be the most important one
If a cell receives a go-ahead signal at the G1 checkpoint, it will usually complete the S, G2, and M phases and divide
If the cell does not receive the go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

54. G0 G1 G1 G1 checkpoint (b) Cell does not receive a go-ahead signal
Fig G0
G1 checkpoint
Figure The G1 checkpoint G1 G1
Cell receives a go-ahead
signal
(b) Cell does not receive a
go-ahead signal

55. 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 concentration of cyclins varies throughout the cell cycle
Cdks are dependent on cyclins, which activate them
When cyclin and Cdk bind together, they form the active molecule MPF that triggers a cell’s passage past the G2 checkpoint into the M phase
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

56. Fig
RESULTS 5 30 4 20 3
% of dividing cells (– )
Protein kinase activity (– ) 2 10 1
Figure How does the activity of a protein kinase essential for mitosis vary during the cell cycle?
100
200
300
400
500
Time (min)

57. (b) Molecular mechanisms that help regulate the cell cycle
Fig b G1 S
Cdk
Cyclin accumulation M
Degraded
cyclin G2 G2
checkpoint
Cdk
Figure Molecular control of the cell cycle at the G2 checkpoint
Cyclin is
degraded
Cyclin
MPF
(b) Molecular mechanisms that help regulate the cell cycle

58. Stop and Go Signs: Internal and External Signals at the Checkpoints
Cyclins and cdks are proteins that can be made by ribosomes with instructions from DNA
You have genes in your DNA that give instructions for how to make these proteins
Gene expression is regulated – each gene can be turned on (causing that protein to be made) or off at different times
Internal and external signals lead to the genes for cyclins and cdks being turned on or off.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

59. Examples of signals
An example of an internal signal (comes from inside the cell) is that kinetochores not attached to spindle microtubules could send a molecular signal that delays anaphase
Some external signals (come from outside the cell) 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

60. Scalpels Petri plate Without PDGF cells fail to divide With PDGF
Fig
Scalpels
Petri
plate
Without PDGF
cells fail to divide
Figure The effect of a growth factor on cell division
With PDGF
cells prolifer-
ate
Cultured fibroblasts
10 µm

61. Outline: Mitosis and the Cell Cycle
Why we need cell division
Stages of the cell cycle
How bacteria are different
Regulating the cell cycle – how does a cell know when to go to the next stage?
Cancer – what happens when the cell cycle is unregulated
Figure 12.2 The functions of cell division

62. 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 stable surface in order to divide
Normal cells make a protein called p53 to stop the cell cycle if there is a problem. In extreme cases, p53 can cause a damaged cell to die (apoptosis)
Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence, and mutations in the gene for p53 are the most common mutations leading to cancer
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

63. Density-dependent inhibition
Fig
Anchorage dependence
Density-dependent inhibition
Density-dependent inhibition
Figure Density-dependent inhibition and anchorage dependence of cell division
25 µm
25 µm
(a) Normal mammalian cells
(b) Cancer cells

64. Loss of Cell Cycle Controls in Cancer Cells
Cancer cells do not respond normally to the body’s control mechanisms; they grow and divide out of control
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

65. A normal cell is converted to a cancerous cell by a process called transformation
Happens due to mutations that change the DNA, making the cell ignore regulatory checkpoints and measures. Mutations in p53 are the most common.
Cancer cells form tumors, masses of abnormal cells within otherwise normal tissue
The lump is called a benign tumor if the cancer cells remain in the same place
Malignant tumors invade surrounding tissues and can metastasize, exporting cancer cells to other parts of the body, where they may form secondary tumors
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

66. Lymph vessel Tumor Blood vessel Cancer cell Glandular tissue
Fig
Lymph
vessel
Tumor
Blood
vessel
Cancer
cell
Glandular
tissue
Metastatic
tumor 1
A tumor grows
from a single
cancer cell. 2
Cancer cells
invade neigh-
boring tissue. 3
Cancer cells spread
to other parts of
the body. 4
Cancer cells may
survive and
establish a new
tumor in another
part of the body.
Figure The growth and metastasis of a malignant breast tumor