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

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Bio 122: Cells and Genetics Evolution and the Foundations of Biology Carbon and the Molecular Diversity of Life A Tour of the Cell Membrane Structure and Function An Introduction to Metabolism

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



Karen S Kabnick,

PhD

Слайд 2Bio 122: Cells and Genetics
Evolution and the Foundations of Biology
Carbon and

the Molecular Diversity of Life
A Tour of the Cell
Membrane Structure and Function
An Introduction to Metabolism
Cellular Respiration and Fermentation
Photosynthesis
Cell Communication
The Cell Cycle
Meiosis and Sexual Life Cycles
Mendel and the Gene Idea
The Chromosomal Basis of Inheritance
The Molecular Basis of Inheritance
Gene Expression: From Gene to Protein
Viruses

Слайд 3Bio 122: Cells and Genetics
Evolution and the Foundations of Biology
Carbon and

the Molecular Diversity of Life
A Tour of the Cell
Membrane Structure and Function
An Introduction to Metabolism
Cellular Respiration and Fermentation
Photosynthesis
Cell Communication
The Cell Cycle
Meiosis and Sexual Life Cycles
Mendel and the Gene Idea
The Chromosomal Basis of Inheritance
The Molecular Basis of Inheritance
Gene Expression: From Gene to Protein
Viruses

Слайд 4Chapter 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

Слайд 5Chapter 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

Слайд 6

Where do cells come from?

Слайд 7Cell division
= cell reproduction
= asexual reproduction

“Every cell from a

cell” –Virchow’s Principle

Слайд 8Asexual reproduction
Offspring genetically identical to original cell or organism (except

mutations)
All genes inherited from one parent

Слайд 9Chapter 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

Слайд 10Bacterial Cell Division: Binary Fission

Слайд 11Bacterial Cell Division: Binary Fission

Слайд 12Bacterial Cell Division: Binary Fission

Слайд 13Prokaryotic chromosomes

Слайд 14Occurs in prokaryotic cells
Two identical cells arise from one cell (except

mutations)
Process
Single circular chromosome duplicates (copies identical except for mutations)
Copies begin to separate from each other
Cell elongates, and chromosomal copies separate further
Plasma membrane grows inward at midpoint to divide into two cells

Asexual Reproduction = binary fission (prokaryotes)

Слайд 15Chapter 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

Слайд 16Asexual Reproduction = mitosis (eukaryotes)
= cell reproduction

Слайд 17Cell division produces new cells in order to:
Produce new unicellular cells


Heal wounds and replace damaged cells/tissues
Grow and develop

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

Слайд 19Overview of a cell cycle:
Three key events in a cell cycle:

Cell

growth and chromosome replication

Chromosomes segregate

Cell division

Слайд 20M phase = Mitosis + cytokinesis
Mitosis: nuclear division

Cytokinesis: cytoplasmic division

Слайд 21Cell Cycle Phases

Слайд 22What do you think would happen if chromosomes did not coil

tightly during mitosis?

Everything would be fine!
DNA would not be properly divvied up!

Слайд 23Eukaryotic Cell Cycle
Interphase
G1 – growth
S – synthesis/replication
G2 – growth
M Phase:

Mitosis and cytokinesis

Слайд 24How Cells Divide
Movies: Salmon Lab, cam.ac.uk, bio.davidson.edu

Слайд 25Mitotic Chromosomes: Human Genome
Image: Lodish, Berk, Zipursky, Matsudaira, Batimore and Darnell. (1999).

Molecular Cell Biology, 4th ed. W.H. Freeman & Co.

Слайд 26?
How is linear DNA packaged into chromosomes?

Слайд 27Levels of DNA Packaging
2-nm double-stranded DNA molecule
11-nm nucleosomes
30-nm chromatin fiber
Organization around

a central scaffold

2

2

Слайд 28Nucleosomes

Слайд 29Karyotype
Diploid = 2n
Haploid = n

Слайд 30Sister chromatids
One duplicated
chromosome
Centromere
Homologous pair of
chromosomes


Paternal chromosome
Maternal chromosome
Non-sister
chromatids

Слайд 31Cell Cycle Phases

Слайд 32Centromere
Chromosome
duplication
Sister
chromatids
Chromosome
distribution
to
daughter
cells

Слайд 33Chromosomes

Слайд 34Before DNA replication in S of cell cycle










Слайд 35After DNA replication










Слайд 36After cell division




















Слайд 37From prophase through metaphase of mitosis, each chromosome has _____ DNA

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

two; one
2n; 1n
homologous; nonhomologous
condensed; decondensed
nonsister chromatid; sister chromatid

Слайд 38Cell Cycle Phases

Слайд 39Interphase
G1 – growth

S – synthesis/replication/centrosome replication

G2 – growth

Слайд 40G2: Prior to Mitosis

Слайд 41Centrosome: MTOC

Слайд 43Cell Cycle Phases


Слайд 44The Stages of Mitosis
Prophase
Prometaphase
Metaphase
Anaphase
Telophase

Слайд 45The Stages of Mitosis: Prophase

Слайд 46The Stages of Mitosis: Prometaphase

Слайд 47The Stages of Mitosis: Metaphase
Alignment of chromosomes along metaphase plate
Not an

actual structure
Future axis of cell division

Слайд 48The Mitotic Spindle


Aster microtubules

Слайд 49Kinetochore

Слайд 50The Stages of Mitosis: Anaphase

Слайд 51Chromosome Movement in Anaphase

Слайд 52Chromosome Movement in Anaphase

Слайд 53The Stages of Mitosis: Telophase

Слайд 54Cytokinesis

Слайд 55Cytokinesis: Plant Cells

Слайд 56Which of the following statements INCORRECTLY matches the cell cycle phase

with the description?

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

Слайд 57Chapter 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

Слайд 58Cell Cycle Phases

Слайд 59Basic 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

Слайд 60Cell Cycle Control
Is DNA copied properly and once?
Are chromosomes aligned properly

and attached to spindle?

Sufficient cell size, nutrients, GFs?

Слайд 61What controls the Cell Cycle?

Слайд 62What controls cell cycle progression? Cyclins and Cyclin-Dependent Kinases
inhibitory
activating

Слайд 63G2/M Checkpoint Progression: Relationship between Cyclin B levels and CDK1 activity
Time
Cyclin
concentration
MPF

activity

M

M

M

S

S

G1

G1

G1

G2

G2

Cyclin B+CDK1 = MPF

Слайд 64Relationship Between CyclinB Levels and CDK1 activity

Слайд 65



Cyclin B is necessary, but NOT sufficient
Inhibitory cdk1 phosphate must be

removed (phosphatase) before MFP is active (active cdk1)

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

Cycle

Слайд 68Cell Cycle Control
Is DNA copied properly and once?
Are chromosomes aligned properly

and attached to spindle?

Sufficient cell size, nutrients, GFs?

Слайд 69The Spindle Checkpoint
Cohesin
Anaphase promoting complex (APC)

Слайд 71DNA Damage (G2/M checkpoint)

Incomplete replication (G2/M checkpoint)

Chromosomes are misaligned (Mitotic/spindle checkpoint)
Internal

Signals that Regulate Cell Cycle Progression

Слайд 72Growth Factors (G1/G0 checkpoint)

Cell Density

Anchorage
External Signals that Regulate Cell Cycle Progression

Слайд 73Growth Factors (G1/G0 checkpoint)

Cell Density

Anchorage
External Signals that Regulate Cell Cycle Progression

Слайд 74Cell Cycle Control
Is DNA copied properly and once?
Are chromosomes aligned properly

and attached to spindle?

Is the cell sufficiently big?
Sufficient growth factors?
Sufficient nutrients?

Слайд 75G1 Checkpoint
G1
G0
G1 checkpoint
G1
Is the cell sufficiently big? Sufficient growth factors? Sufficient

nutrients?

Слайд 76The Mitotic Cell Cycle
G1/G2 = Gap or Growth Phases

S = Synthesis

– when DNA is replicated

Interphase = G1/S/G2

Слайд 77Growth Factor Regulation of Cell Division
Cultured fibroblasts
Without PDGF
(platelet-derived
growth factor)
With PDGF
10

µm

Слайд 78Cell Cycle Control
PDGF

Слайд 79G1 checkpoint
Control
system
M
S
G2
G1
Receptor
protein
Signal
transduction
pathway
Relay
proteins
Plasma membrane
Growth factor

Слайд 81Growth Factors

Cell Density

Anchorage
External Signals that Regulate Cell Cycle Progression

Слайд 82Effect of Cell Density on Cell Division

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

Слайд 84Growth Factors

Cell Density

Anchorage
External Signals that Regulate Cell Cycle Progression

Слайд 85Anchorage Dependence and Cell Division
Growth Factors
Cell Division


Слайд 86Chapter 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

Слайд 87Cancer: 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

Слайд 88Development of Cancer is a Multi-Step Process
Figure 20-11 Molecular Biology of

the Cell (© Garland Science 2008)

Слайд 89Loss of Density Dependence = Loss of Contact Inhibition

Слайд 90Development of Cancer is a Multi-Step Process
Figure 20-11 Molecular Biology of

the Cell (© Garland Science 2008)


Слайд 91Figure 20-11 Molecular Biology of the Cell (© Garland Science 2008)
Benign

Tumor

Malignant Tumor

Слайд 92Cancer Growth and Metastasis

Слайд 93Cancer Growth and Metastasis

Слайд 94Does a mutation in any gene lead to cancer?
Proto-oncogenes
Tumor Suppressor Genes

Слайд 96Proto-oncogenes normally promote cell growth in response to proper signals





Mutated proto-oncogenes

= oncogenes

Oncogenes are overactive: always promote cell-growth (gasoline tank always full)




Activated Proto-oncogenes Promote Cancer

cell

proto-oncogene

Слайд 97What role do oncogenes play?
Proto-oncogenes normally promote cell division under proper

conditions
Oncogenes promote cell division all the time (constitutively)

Слайд 98
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)



GF

Ras

Слайд 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

Слайд 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

Слайд 101Inactivated Tumor Suppressor Genes Lead to Cancer
Tumor Suppressor (TS) genes normally

inhibit cell growth





Mutations that inactivate TS genes, prevent their ability to inhibit cell growth





cell

TS gene

Слайд 102What 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

Слайд 103Example: Rb

Слайд 104Example: p53
Adapted from Zhou and Elledge. (2000) Nature 408:433




Слайд 105Example: p53

Слайд 106Example: p53




Слайд 109Figure 9.4 The Biology of Cancer (© Garland Science 2007)
TP53 =

p53

Слайд 110Cancer 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

Слайд 111Which of the following is NOT a typical trait of cancerous

cells that makes them different from normal somatic cells?

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

Слайд 112Chapter 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.


Слайд 113Chapter 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

Слайд 114Bio 122: Cells and Genetics
Evolution and the Foundations of Biology
Carbon and

the Molecular Diversity of Life
A Tour of the Cell
Membrane Structure and Function
An Introduction to Metabolism
Cellular Respiration and Fermentation
Photosynthesis
Cell Communication
The Cell Cycle
Meiosis and Sexual Life Cycles
Mendel and the Gene Idea
The Chromosomal Basis of Inheritance
The Molecular Basis of Inheritance
Gene Expression: From Gene to Protein
Viruses

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