1. Chapter 12
The Cell Cycle

2. 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

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

4. 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

5. 100 µm (a) Reproduction Fig. 12-2a
Figure 12.2 The functions of cell division
(a) Reproduction

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

7. 20 µm (c) Tissue renewal Fig. 12-2c
Figure 12.2 The functions of cell division
(c) Tissue renewal

8. I. Cell division genetics
Mitosis - most cell division results in daughter cells with identical genetic information (DNA)
Meiosis - Special type of division produces nonidentical daughter cells, gametes (sperm and egg cells)

9. II. Organization of the Genetic Material
All the DNA in a cell constitutes the cell’s genome
Can consist of a single DNA molecule (prokaryotic cells) or a number of DNA molecules (eukaryotic cells)
DNA molecules in a cell are packaged into chromosomes

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

11. Every species has a set # of chroms in each nucleus
Somatic cells (nonreproductive (body) cells) have 2 sets of chroms (diploid = 2n)
Gametes (reproductive cells: sperm and eggs) have half as many chroms (monoploid = n)
Eukaryotic chroms consist of chromatin (complex of DNA and protein that condenses during cell division)

12. III. Distribution of Chroms During Euk Cell Division
DNA is replicated and the chroms condense
Each duplicated chrom makes two sister chromatids, which separate during cell division
Centromere = where the two chromatids are most closely attached

13. 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

14. Eukaryotic cell division consists of:
Mitosis, the division of the nucleus
Cytokinesis, the division of the cytoplasm

15. The cell cycle consists of
IV. Phases of Cell Cycle
The cell cycle consists of
Mitotic (M) phase (mitosis and cytokinesis)
Interphase (cell growth and copying of chromosomes)

16. Interphase (90% of cycle) is divided into:
G1 phase (“first gap”)
S phase (“synthesis”)
G2 phase (“second gap”)
Cell grows during all phases, but chroms are duplicated only during S phase

17. 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

18. Mitosis is 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.

19. 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

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

21. 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

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

23. Prophase = assembly of spindle microtubules begins in centrosome
V. The Mitotic Spindle
An apparatus of microtubules that controls chrom movement during mitosis
Prophase = assembly of spindle microtubules begins in centrosome
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.

24. Aster (a radial array of microtubules) extends from each centrosome
The spindle includes the centrosomes, the spindle microtubules, and the asters

25. Prometaphase = some spindle microtubules attach to the kinetochores of chromosomes and begin to move the chromosomes
Metaphase = chroms are all lined up at the metaphase plate (midway point between spindle’s two poles)

26. 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

27. Microtubules shorten by depolymerizing at their kinetochore ends
Anaphase = sister chromatids separate and move along the kinetochore microtubules toward opposite ends of the cell
Microtubules shorten by depolymerizing at their kinetochore ends
For the Cell Biology Video Microtubules in Anaphase, go to Animation and Video Files.

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

29. 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

30. Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell
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.

31. VI. Cytokinesis
Animal cells = cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
Plant cells = a cell plate forms during cytokinesis

32. (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)

33. (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)

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

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

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

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

38. 10 µm Cell plate 5 Telophase Fig. 12-10e
Figure Mitosis in a plant cell 5
Telophase

39. Mitosis - Andersen (13 min)
For the Cell Biology Video Nuclear Envelope Formation, go to Animation and Video Files.

40. Prokaryotes (bacteria and archaea) reproduce by binary fission
VII. Binary Fission
Prokaryotes (bacteria and archaea) reproduce by binary fission
Chrom replicates and the two daughter chromosomes actively move apart
Equal division of cytoplasm

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
Origin
Origin
Figure Bacterial cell division by binary fission

42. VIII. The Evolution of Mitosis
Mitosis probably evolved from binary fission (pros before eus)
Some protists exhibit types of cell division that seem intermediate between binary fission and mitosis

43. Bacterial chromosome (a) Bacteria Chromosomes Microtubules
Fig ab
Bacterial
chromosome
(a) Bacteria
Chromosomes
Microtubules
Figure A hypothetical sequence for the evolution of mitosis
Intact nuclear
envelope
(b) Dinoflagellates

44. Kinetochore microtubule Intact nuclear envelope (c) Diatoms and yeasts
Fig cd
Kinetochore
microtubule
Intact nuclear
envelope
(c) Diatoms and yeasts
Kinetochore
microtubule
Figure A hypothetical sequence for the evolution of mitosis
Fragments of
nuclear envelope
(d) Most eukaryotes

45. IX. Cell cycle regulatation
Frequency of cell division varies with type of cell
Differences result from regulation at the molecular level

46. X. Evidence for Cytoplasmic Signals
Cell cycle appears to be driven by specific chemical signals present in the cytoplasm
When mammalian cells at different phases of the cell cycle were fused to form a single cell with two nuclei, the “early” stage jumped ahead to the “later” stage

47. 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?

48. XI. Cell Cycle Control System
Events of the cell cycle are directed by a cell cycle control system (like a clock)
Regulated by both internal and external controls
Clock has specific checkpoints where the cell cycle stops until a go-ahead signal is received

49. 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

50. G1 checkpoint seems to be the most important
If cell gets a go-ahead signal at G1, it will usually complete the S, G2, and M phases and divide
If cell does not receive a go-ahead signal, it will exit the cycle, switching into a nondividing state called the G0 phase

51. 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

52. A. Cyclins and Cyclin-Dependent Kinases
Two types of regulatory proteins in cell cycle control: cyclins and cyclin-dependent kinases (Cdks)
Activity of both 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

53. 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)

54. M G1 S G2 M G1 S G2 M G1 Fig. 12-17 MPF activity Cyclin concentration
Time
(a) Fluctuation of MPF activity and cyclin concentration during
the cell cycle G1 S
Cdk
Figure Molecular control of the cell cycle at the G2 checkpoint
Cyclin accumulation M
Degraded
cyclin G2 G2
Cdk
Cyclin is
degraded
checkpoint
Cyclin
MPF
(b) Molecular mechanisms that help regulate the cell cycle

55. B. Internal and External Signals
Internal signal = kinetochores not attached to spindle microtubules send a molecular signal that delays anaphase
External signals = growth factors, proteins released by certain cells that stimulate other cells to divide
Ex. platelet-derived growth factor (PDGF) stimulates the division of human fibroblast cells (make collagen and ECM) in culture

56. 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

57. Ex. density-dependent inhibition = crowded cells stop dividing
Ex. Animal cells exhibit anchorage dependence = cells must be attached to a substratum in order to divide
Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

58. 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

59. XII. Loss of Cell Cycle Controls in Cancer Cells
Do not respond normally to the body’s control mechanisms
Cancer cells may not need growth factors to grow and divide:
May make their own growth factor
May convey a growth factor’s signal w/o the growth factor
May have an abnormal cell cycle control system

60. Transformation = normal cell is converted to a cancerous cell
Cancer cells form tumors (masses of abnormal cells w/in normal tissue)
Benign tumor = abnormal cells remain at the original site
Malignant tumors = invade surrounding tissues and can metastasize (exporting cancer cells to other parts of the body, where they may form secondary tumors)

61. 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

62. Fig. 12-UN2

63. Fig. 12-UN5

64. Fig. 12-UN6

65. 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

66. 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