Evolution and the foundations of biology. Cells and genetics. (Сhapter 9)

1. BIO 122: Cells and Genetics Chapter 9: The Cell Cycle

Karen S Kabnick, PhD

2. Bio 122: Cells and Genetics

1. Evolution and the Foundations of Biology
2. Carbon and the Molecular Diversity of Life
3. A Tour of the Cell
4. Membrane Structure and Function
5. An Introduction to Metabolism
6. Cellular Respiration and Fermentation
7. Photosynthesis
8. Cell Communication
9. The Cell Cycle
10. Meiosis and Sexual Life Cycles
11. Mendel and the Gene Idea
12. The Chromosomal Basis of Inheritance
13. The Molecular Basis of Inheritance
14. Gene Expression: From Gene to Protein
15. Viruses

3. Bio 122: Cells and Genetics

1. Evolution and the Foundations of Biology
2. Carbon and the Molecular Diversity of Life
3. A Tour of the Cell
4. Membrane Structure and Function
5. An Introduction to Metabolism
6. Cellular Respiration and Fermentation
7. Photosynthesis
8. Cell Communication
9. The Cell Cycle
10. Meiosis and Sexual Life Cycles
11. Mendel and the Gene Idea
12. The Chromosomal Basis of Inheritance
13. The Molecular Basis of Inheritance
14. Gene Expression: From Gene to Protein
15. Viruses

4. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

5. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

6. Where do cells come from?

7. “Every cell from a cell” –Virchow’s Principle

Cell division
= cell reproduction
= asexual reproduction

8.

Asexual reproduction
• Offspring genetically identical to original cell or
organism (except mutations)
• All genes inherited from one parent

9. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

10. Bacterial Cell Division: Binary Fission

11. Bacterial Cell Division: Binary Fission

12. Bacterial Cell Division: Binary Fission

13.

Prokaryotic chromosomes

14. Asexual Reproduction = binary fission (prokaryotes)

• Occurs in prokaryotic cells
• Two identical cells arise from one cell (except
mutations)
• Process
1. Single circular chromosome duplicates (copies identical
except for mutations)
2. Copies begin to separate from each other
3. Cell elongates, and chromosomal copies separate
further
4. Plasma membrane grows inward at midpoint to divide
into two cells

15. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

16.

Asexual Reproduction = mitosis (eukaryotes)
= cell reproduction

17. Cell division produces new cells in order to:

• Produce new unicellular cells
• Heal wounds and replace
damaged cells/tissues
• Grow and develop

18. What needs to happen for cell division to occur normally?

19. Overview of a cell cycle:

Three key events in a cell
cycle:
Cell growth and
chromosome replication
Chromosomes segregate
Cell division

20.

M phase = Mitosis + cytokinesis
Mitosis: nuclear division
Cytokinesis: cytoplasmic division

21. Cell Cycle Phases

22. What do you think would happen if chromosomes did not coil tightly during mitosis?

A. Everything would be fine!
B. DNA would not be properly divvied up!
0%
A.
0%
B.

23. Eukaryotic Cell Cycle

• Interphase
– G1 – growth
– S – synthesis/replication
– G2 – growth
• M Phase: Mitosis and cytokinesis

24. How Cells Divide

Movies: Salmon Lab, cam.ac.uk, bio.davidson.edu

25. Mitotic Chromosomes: Human Genome

Image: Lodish, Berk, Zipursky, Matsudaira, Batimore and Darnell. (1999). Molecular Cell Biology, 4th ed. W.H. Freeman & Co.

26.

How is linear DNA packaged into chromosomes?
?

27. Levels of DNA Packaging

22
2-nm double-stranded DNA molecule
11-nm nucleosomes
30-nm chromatin fiber
Organization around a central scaffold

28.

Nucleosomes

29. Karyotype

Diploid = 2n
Haploid = n

30.

Homologous pair of
chromosomes
Paternal
chromosome
Maternal
chromosome
Non-sister
chromatids
Sister chromatids
Centromere
One duplicated
chromosome

31. Cell Cycle Phases

32.

Chromosome
duplication
Centromere
Sister
chromatids
Chromosome
distribution
to
daughter
cells

33. Chromosomes

34. Before DNA replication in S of cell cycle

35. After DNA replication

36. After cell division

37. From prophase through metaphase of mitosis, each chromosome has _____ DNA molecules, while from anaphase through telophase of mitosis, each chromosome has _____ DNA molecule(s).

A.
B.
C.
D.
E.
two; one
2n; 1n
homologous; nonhomologous
condensed; decondensed
nonsister chromatid; sister
0% chromatid
0%
0%
A.
B.
C.
0%
0%
D.
E.

38. Cell Cycle Phases

39. Interphase

• G1 – growth
• S – synthesis/replication/centrosome
replication
• G2 – growth

40. G2: Prior to Mitosis

41.

Centrosome: MTOC

42.

43. Cell Cycle Phases

44. The Stages of Mitosis

Prophase
Prometaphase
Metaphase
Anaphase
Telophase

45. The Stages of Mitosis: Prophase

46. The Stages of Mitosis: Prometaphase

47. The Stages of Mitosis: Metaphase

Alignment of
chromosomes along
metaphase plate
– Not an actual structure
– Future axis of cell
division

48. The Mitotic Spindle

Aster microtubules

49. Kinetochore

50. The Stages of Mitosis: Anaphase

51. Chromosome Movement in Anaphase

52.

Chromosome Movement in Anaphase

53. The Stages of Mitosis: Telophase

54. Cytokinesis

55. Cytokinesis: Plant Cells

56. Which of the following statements INCORRECTLY matches the cell cycle phase with the description?

A. S phase: DNA of each chromosome is replicated
B. Telophase: each chromosome has one double-stranded DNA
molecule
C. Metaphase: kinetochore on the chromosome loses its attachment
to spindle microtubulesDuring G1, the DNA in the nuclear
chromosomes is not all highly condensed.
D. G1: nuclear chromosomal DNA is not all highly condensed
E. Metaphase: each chromosome consists of two
double-stranded DNA helices linked together at a
centromere
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.

57. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

58. Cell Cycle Phases

59. Basic Problems in Cell Cycle Control

• DNA must be replicated once per cell cycle
• Sister chromatids must segregate accurately
• Cell division must be coupled to growth and
conditions
• Events must be coordinated

60. Cell Cycle Control

Sufficient cell size, nutrients, GFs?
Are chromosomes
aligned properly and
attached to spindle?
Is DNA copied properly and once?

61. What controls the Cell Cycle?

62. What controls cell cycle progression? Cyclins and Cyclin-Dependent Kinases

inhibitory
activating

63. G2/M Checkpoint Progression: Relationship between Cyclin B levels and CDK1 activity

M
G1
S
G2
M
G1
S
MPF activity
Cyclin
concentration
Time
Cyclin B+CDK1 = MPF
G2
M
G1

64. Relationship Between CyclinB Levels and CDK1 activity

65.

Cyclin B is necessary, but NOT sufficient
Inhibitory cdk1 phosphate must be
removed (phosphatase) before MFP
is active (active cdk1)

66.

cdk1

67. Different CDK/Cyclin Complexes are Important at Different Points in the Cell Cycle

68. Cell Cycle Control

Sufficient cell size, nutrients, GFs?
Are chromosomes
aligned properly and
attached to spindle?
Is DNA copied properly and once?

69. The Spindle Checkpoint

Anaphase promoting complex (APC)
Cohesin

70.

71. Internal Signals that Regulate Cell Cycle Progression

• DNA Damage (G2/M checkpoint)
• Incomplete replication (G2/M checkpoint)
• Chromosomes are misaligned (Mitotic/spindle
checkpoint)

72. External Signals that Regulate Cell Cycle Progression

• Growth Factors (G1/G0 checkpoint)
• Cell Density
• Anchorage

73. External Signals that Regulate Cell Cycle Progression

• Growth Factors (G1/G0 checkpoint)
• Cell Density
• Anchorage

74. Cell Cycle Control

Is the cell sufficiently big?
Sufficient growth factors?
Sufficient nutrients?
Are chromosomes
aligned properly and
attached to spindle?
Is DNA copied properly and once?

75. G1 Checkpoint

Is the cell sufficiently big? Sufficient growth factors? Sufficient
nutrients?
G0
G1 checkpoint
G1
G1

76. The Mitotic Cell Cycle

G1/G2 = Gap
or Growth
Phases
S = Synthesis
– when DNA
is replicated
Interphase =
G1/S/G2

77. Growth Factor Regulation of Cell Division

Without PDGF
(platelet-derived
growth factor)
With PDGF
Cultured fibroblasts
10 µm

78. Cell Cycle Control

PDGF

79.

Growth factor
Plasma membrane
Receptor
protein
Signal
transduction
pathway
Relay
proteins
G1 checkpoint
Control
system
G1
M
G2
S

80.

81. External Signals that Regulate Cell Cycle Progression

• Growth Factors
• Cell Density
• Anchorage

82. Effect of Cell Density on Cell Division

83. Effect of Cell Density on Cell Division => contact inhibition

Effect of Cell Density on Cell Division
=> contact inhibition

84. External Signals that Regulate Cell Cycle Progression

• Growth Factors
• Cell Density
• Anchorage

85. Anchorage Dependence and Cell Division

Growth Factors
Cell Division

86. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

87. Cancer: Breaching the Controls that Maintain Normal Homeostasis

Do not require growth factors
No density-dependent inhibition
Anchorage independent
Ignore DNA damage (G2/M checkpoint)
Enter M (pass G2/M checkpoint) with
incompletely replicated DNA
• Bypass M/spindle checkpoint with misaligned
chromosomes

88. Development of Cancer is a Multi-Step Process

Figure 20-11 Molecular Biology of the Cell (© Garland Science 2008)

89. Loss of Density Dependence = Loss of Contact Inhibition

90. Development of Cancer is a Multi-Step Process

Figure 20-11 Molecular Biology of the Cell (© Garland Science 2008)

91.

Benign Tumor
Malignant Tumor
Figure 20-11 Molecular Biology of the Cell (© Garland Science 2008)

92. Cancer Growth and Metastasis

93. Cancer Growth and Metastasis

94. Does a mutation in any gene lead to cancer?

• Proto-oncogenes
• Tumor Suppressor Genes

95.

96.

Activated Proto-oncogenes Promote Cancer
• Proto-oncogenes normally promote cell growth in
response to proper signals
cell
proto-oncogene
• Mutated proto-oncogenes = oncogenes
• Oncogenes are overactive: always promote cellgrowth (gasoline tank always full)

97. What role do oncogenes play?

• Proto-oncogenes normally promote cell
division under proper conditions
– Oncogenes promote cell division all the time
(constitutively)

98. What role do oncogenes play?

– Oncogenes promote cell division all the time
(constitutively)
– Example: mutated Ras
(oncogene)
G
F
Proto-oncogenes normally promote cell
division under the proper conditions
Ras

99. What role do oncogenes play?

Proto-oncogenes normally promote cell
division under the proper conditions
– Oncogenes promote cell division all the time
(constitutively)
– Example: mutated Ras
(oncogene)
Ras

100. What role do oncogenes play?

Proto-oncogenes normally promote cell
division under the proper conditions
– Oncogenes promote cell division all the time
(constitutively)
– Example: mutated Ras
(oncogene)
Ras

101.

Inactivated Tumor Suppressor Genes
Lead to Cancer
• Tumor Suppressor (TS) genes normally inhibit cell
growth
cell
TS gene
• Mutations that inactivate TS genes, prevent their
ability to inhibit cell growth

102. What role do oncogenes and tumor suppressor genes play?

• Proto-oncogenes normally promote cell division
under the proper conditions
– Oncogenes promote cell division all the time
(constitutively)
– Example: Ras, src
• Normal tumor suppressor genes inhibit cell
division unless conditions are right
– Mutant tumor suppressor genes lose their ability to
inhibit cell division
– Examples: Rb, p53, BRCA1, BRCA2

103.

Example: Rb

104. Example: p53

Adapted from Zhou and Elledge. (2000) Nature 408:433

105. Example: p53

106. Example: p53

107.

108.

109.

TP53 = p53
Figure 9.4 The Biology of Cancer (© Garland Science 2007)

110. Cancer Treatment

• Radiation – damages DNA
– Some cancer cells are more susceptible to death from
DNA damage – lost the ability to properly repair
• Chemotherapy – drugs toxic to dividing cells
– Side effects due to damage to normally dividing cells
• Directed therapies – specific to the relevant mutation
– Few exist
– No one cure for all cancer

111. Which of the following is NOT a typical trait of cancerous cells that makes them different from normal somatic cells?

A. Cancer cells often deactivate their apoptosis
systems.
B. Cancerous cells are not as sensitive to contact
inhibition.
C. The cell cycle often proceeds faster in cancer cells.
D. Cancer cells are more mobile and less dependent
on anchorage.
E. Cancer cells have more effective DNA repair
activities.
0%
A.
0%
0%
B.
C.
0%
0%
D.
E.

112. Chapter 9: Learning Objectives

• What are key structures of chromosomes, especially as they related to mitosis?
• What are the stages of the cell cycle? What happens in each stage? What is the
structure of DNA at different stages?
• Haploidy? Diploidy?
• Compare and contrast bacterial fission with eukaryotic cell cycle and mitosis.
• How is the cell cycle controlled? What role do cyclins/CDKs play? How is their
activity controlled?
• What functions are monitored at each checkpoint?
• What internal and external factors are required for cell cycle progression?
• What role do cohesins play in mitosis? What role does their degradation play?
• How does cytokinesis differ in animal and plant cells?
• How can the cell fail to be controlled properly? What does this lead to?
• How do oncogenes and mutant tumor suppressor genes promote cancer
development? Understand p53 and ras is the context of cancer progression.

113. Chapter 9: The Cell Cycle

• Cell Replication
– Prokaryotic: binary fission
– Eukaryotic: cell cycle and mitosis
• Controlling the Eukaryotic Cell Cycle
• Failure to Control the Eukaryotic Cell Cycle:
Cancer

114. Bio 122: Cells and Genetics

1. Evolution and the Foundations of Biology
2. Carbon and the Molecular Diversity of Life
3. A Tour of the Cell
4. Membrane Structure and Function
5. An Introduction to Metabolism
6. Cellular Respiration and Fermentation
7. Photosynthesis
8. Cell Communication
9. The Cell Cycle
10. Meiosis and Sexual Life Cycles
11. Mendel and the Gene Idea
12. The Chromosomal Basis of Inheritance
13. The Molecular Basis of Inheritance
14. Gene Expression: From Gene to Protein
15. Viruses