1. The Cell Cycle
Chapter 12

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. 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

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

5. 12.1: Cell division produces 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)

6. 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

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

8. 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

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 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

10. 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

11. Eukaryotic cell division consists of:
Mitosis – division of the nuclear DNA
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

12. 12.2: The mitotic phase alternates with interphase in the cell cycle
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)

13. Interphase (about 90% of the cell cycle) is divided into three 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

14. 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

15. Mitosis is conventionally divided into five phases:
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
Cytokinesis occurs during late telophase
For the Cell Biology Video Myosin and Cytokinesis, go to Animation and Video Files.

16. 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

17. 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

18. The Mitotic Spindle
The mitotic spindle is composed of microtubules which 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.

19. An aster (a radial array of short microtubules) extends from each centrosome
The spindle includes the centrosomes, the spindle microtubules, and the asters

20. During prometaphase, some spindle microtubules attach to the centromere kinetochores of the 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

21. 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

22. 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.

23. EXPERIMENT RESULTS CONCLUSION Kinetochore Spindle pole Mark Chromosome
Fig. 12-8
EXPERIMENT
Kinetochore
Spindle
pole
Mark
RESULTS
Figure 12.8 At which end do kinetochore microtubules shorten during anaphase?
CONCLUSION
Chromosome
movement
Kinetochore
Motor
protein
Tubulin
subunits
Microtubule
Chromosome

24. 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

25. Nonkinetochore microtubules from opposite poles overlap and push against each other, elongating the cell
In telophase, the nuclear envelope reforms around genetically identical daughter nuclei at opposite ends of the cell
For the Cell Biology Video Microtubules in Cell Division, go to Animation and Video Files.

26. Cytokinesis
In animal cells, cytokinesis occurs by a process known as cleavage, forming a cleavage furrow
In plant cells, a cell plate forms during cytokinesis

27. 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

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

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

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

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

32. 10 µm Cell plate 5 Telophase Fig. 12-10e
Figure Mitosis in a plant cell 5
Telophase

33. 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

34. 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

35. 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

36. 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

37. 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

38. The Evolution of Mitosis
Since prokaryotes evolved before eukaryotes, mitosis probably evolved from binary fission
Certain protists exhibit types of cell division that appears to be an intermediate between binary fission and mitosis

39. 12.3: Control of the Cell Cycle
The frequency of cell division varies depending on the type of cell
These differences result from regulation of the cell cycle at the molecular level

40. 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

41. 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

42. 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

43. 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

44. 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

45. 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

46. (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

47. 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

48. 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

49. 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

50. 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

51. Cancer cells exhibit neither density-dependent inhibition nor anchorage dependence

52. Cancer: Is the Loss of Control of the Cell Cycle
Cancer cells do not respond 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 relay a growth factor’s signal without the presence of the growth factor
They may have an abnormal cell cycle control system

53. 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

54. 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

55. REVIEW

56. 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

57. Fig. 12-UN2

58. Fig. 12-UN3

59. Fig. 12-UN4

60. Fig. 12-UN5

61. Fig. 12-UN6

62. 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

63. 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