1. Chapter 12
The Cell Cycle

2. You should now be able to:
Describe the structural organization of the prokaryotic genome and the eukaryotic genome
List the phases of the cell cycle; describe the sequence of events during each phase
List the phases of mitosis and describe the events characteristic of each phase
Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

3. Compare cytokinesis in animals and plants
Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission
Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls
Distinguish between benign, malignant, and metastatic tumors
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

4. Concept 12. 1: Cell division results in
Concept 12.1: Cell division results in genetically identical daughter cells
Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
Concept 12.3: The eukaryotic cell cycle is regulated by a molecular control system

5. Overview: The Key Roles of Cell Division
The ability of organisms to reproduce best distinguishes living things from nonliving matter
The continuity of life is based on the reproduction of cells, or cell division
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

6. Fig. 12-1
Figure 12.1 How do a cell’s chromosomes change during cell division?

7. Multicellular organisms depend on cell division for:
In unicellular organisms, division of one cell reproduces the entire organism
Multicellular organisms depend on cell division for:
Development from a fertilized cell
Growth
Repair
Cell division is an integral part of the cell cycle, the life of a cell from formation to its own division
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

8. 100 µm (a) Reproduction Fig. 12-2a
Figure 12.2 The functions of cell division
(a) Reproduction

9. (b) Growth and development
Fig. 12-2b
200 µm
Figure 12.2 The functions of cell division
(b) Growth and development

10. 20 µm (c) Tissue renewal Fig. 12-2c
Figure 12.2 The functions of cell division
(c) Tissue renewal

11. Concept 12.1: Cell division results in genetically identical daughter cells
Most cell division results in daughter cells with identical genetic information, DNA
A special type of division produces nonidentical daughter cells (gametes, or sperm and egg cells)
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12. Cellular 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
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13. Fig. 12-3
Figure 12.3 Eukaryotic chromosomes
20 µm

14. Somatic cells (nonreproductive cells) have two sets of chromosomes
Every eukaryotic species has a characteristic number of chromosomes in each cell nucleus
Somatic cells (nonreproductive cells) have two sets of chromosomes
Gametes (reproductive cells: sperm and eggs) have half as many chromosomes as somatic cells
Eukaryotic chromosomes consist of chromatin, a complex of DNA and protein that condenses during cell division
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15. Distribution of Chromosomes During Eukaryotic 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

16. 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

17. 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
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18. Concept 12.2: The mitotic phase alternates with interphase in the cell cycle
In 1882, the German anatomist Walther Flemming developed dyes to observe chromosomes during mitosis and cytokinesis
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

19. Phases of the Cell Cycle
The cell cycle consists of
Mitotic (M) phase (mitosis and cytokinesis)
Interphase (cell growth and copying of chromosomes in preparation for cell division)
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20. 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

21. S (DNA synthesis) G1 Cytokinesis G2 Mitosis
Fig. 12-5
INTERPHASE S
(DNA synthesis) G1
Cytokinesis G2
Mitosis
Figure 12.5 The cell cycle
MITOTIC
(M) PHASE

22. BioFlix: Mitosis (~60 MB)
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 (~60 MB)
better to see at
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

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

24. 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

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

26. 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

27. 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

28. An aster (a radial array of short microtubules) extends from each centrosome
The spindle includes the centrosomes, the spindle microtubules, and the asters
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

29. During prometaphase, some spindle microtubules attach to the kinetochores 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

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

31. 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

32. EXPERIMENT Kinetochore Spindle pole Mark RESULTS Fig. 12-8a
Figure 12.8 At which end do kinetochore microtubules shorten during anaphase?
RESULTS

33. Chromosome movement Kinetochore Tubulin Motor Subunits Microtubule
Fig. 12-8b
CONCLUSION
Chromosome
movement
Kinetochore
Tubulin
Subunits
Motor
protein
Microtubule
Figure 12.8 At which end do kinetochore microtubules shorten during anaphase?
Chromosome

34. 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

35. 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

36. Video: Sea Urchin (Time Lapse)
Video: Animal Mitosis
Video: Sea Urchin (Time Lapse)
For the Cell Biology Video Nuclear Envelope Formation, go to Animation and Video Files.
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

37. (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)

38. (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)

39. 10 µm Fig. 12-10 Nucleus Chromatin condensing Nucleolus Chromosomes
Cell plate
Figure Mitosis in a plant cell 1
Prophase 2
Prometaphase 3
Metaphase 4
Anaphase 5
Telophase

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

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

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

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

44. 10 µm Cell plate 5 Telophase Fig. 12-10e
Figure Mitosis in a plant cell 5
Telophase

45. 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

46. 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

47. 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

48. 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

49. 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

50. 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

51. Fig. 12-12 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

52. The frequency of cell division varies with the type of cell
Concept 12.3: 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
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53. Evidence for Cytoplasmic Signals
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

54. 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?

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

56. 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

57. 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

58. 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

59. 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

60. 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)

61. (a) Fluctuation of MPF activity and cyclin concentration during
Fig a M G1 S G2 M G1 S G2 M G1
MPF activity
Cyclin
concentration
Figure Molecular control of the cell cycle at the G2 checkpoint
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle

62. (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

63. 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

64. 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

65. 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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

66. 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

67. Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence
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68. Loss of Cell Cycle Controls in Cancer Cells
Cancer cells do not respond normally to the body’s control mechanisms
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

69. A normal cell is converted to a cancerous cell by a process called transformation
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
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

70. 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

71. 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

72. Fig. 12-UN2

73. Fig. 12-UN3

74. Fig. 12-UN4

75. Fig. 12-UN5

76. Fig. 12-UN6

77. You should now be able to:
Describe the structural organization of the prokaryotic genome and the eukaryotic genome
List the phases of the cell cycle; describe the sequence of events during each phase
List the phases of mitosis and describe the events characteristic of each phase
Draw or describe the mitotic spindle, including centrosomes, kinetochore microtubules, nonkinetochore microtubules, and asters
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings

78. Compare cytokinesis in animals and plants
Describe the process of binary fission in bacteria and explain how eukaryotic mitosis may have evolved from binary fission
Explain how the abnormal cell division of cancerous cells escapes normal cell cycle controls
Distinguish between benign, malignant, and metastatic tumors
Copyright © 2008 Pearson Education, Inc., publishing as Pearson Benjamin Cummings