Download Lecture 13 Notes CH.12

BIOLOGY 101
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CHAPTER 12: The Cell Cycle:
The Key Roles of Cell Division
The Cell Cycle:
The Key Roles of Cell Division
CONCEPTS:
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12.1 Most cell division results in genetically identical daughter cells
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12.2 The mitotic phase alternates with interphase in the cell cycle
•
12.3 The eukaryotic cell cycle is regulated by a molecular control system
Can you describe or explain these processes?
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
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In both prokaryotes and eukaryotes, most cell division involves the distribution of identical genetic
material—DNA—to two daughter cells.
o The exception is meiosis, the special type of eukaryotic cell division that can produce sperm and
eggs.
There is a high level of fidelity with which DNA is passed along, without dilution, from one generation to
the next.
A dividing cell duplicates its DNA, allocates the two copies to opposite ends of the cell, and only then
splits into daughter cells
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
•
The process of somatic cell division involves three primary events:
1.
DNA Replication
2.
Sorting of Chromosomes into new nuclei
3.
Cell division
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
•
A cell’s genetic information, packaged as DNA, is called its genome.
o
In prokaryotes, the genome is often a single long circular DNA molecule.
o
In eukaryotes, the genome consists of a number of DNA molecules (chromosomes).
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
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A human cell must copy or replicate about 2m of DNA and separate the two copies so that each
daughter cell ends up with a complete genome.
DNA molecules are packaged into chromosomes.
Every eukaryotic chromosome consists
of one long, linear DNA molecule
associated with many proteins called
histones. Together, the complex is
referred to as chromatin.
o
The proteins maintain the structure
of the chromosome and help control
the activity of the genes.
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
•
Before a cell can divide into two daughter cells the DNA must be replicated
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Semiconservative DNA Replication creates identical copies of
chromosomes
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
•
Before a cell can divide into two daughter cells the DNA must be replicated
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Semiconservative DNA Replication creates identical copies of
chromosomes
•
After a cell duplicates all its chromosomes, it must sort them into the two
daughter cells
The Cell Cycle:
The Key Roles of Cell Division
12.1 Most cell division results in genetically identical daughter cells
•
Each eukaryotic species has a characteristic number of chromosomes in each cell nucleus.
o
Human somatic cells (all body cells except sperm and egg)
have 46 chromosomes, made up of two sets of 23 (one from
each parent).
o
Human reproductive cells or gametes (sperm or eggs) have
one set of 23 chromosomes, half the number in a somatic
cell.
✓
The number of chromosomes in somatic cells varies widely
among species
The Cell Cycle:
Most cell division results in genetically identical daughter cells
12.1 Chromosomes are distributed during eukaryotic cell division
•
When a cell is not dividing, each chromosome is in the form of a long, thin chromatin fiber.
•
Before cell division but after DNA replication, the chromatin condenses, coiling and folding to make a
smaller package that is easier to manage and sort
The Cell Cycle:
Most cell division results in genetically identical daughter cells
12.1 Chromosomes are distributed during eukaryotic cell division
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Humans are diploid, meaning that they have two copies of each chromosome – one set coming from
each parent
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Theses sets from each parent are called Homologous Chromosomes. They are each parent’s version of
the particular chromosome. Humans have 23 sets of chromosomes (46 total)
The Cell Cycle:
Most cell division results in genetically identical daughter cells
12.1 Chromosomes are distributed during eukaryotic cell division
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Sister Chromatids are identical copies of a chromosome – made during DNA replication
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Centromere is the part of the chromosome where sister chromatids are linked; the kinetochore is
associated with the centromere.
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Kinetochore is the structure that mitotic spindles connect with to pull sister chromatids apart
(they *connect* the spindles to the *core* and are associated with the centromere)
The Cell Cycle:
Most cell division results in genetically identical daughter cells
12.1 Chromosomes are distributed during eukaryotic cell division
•
Sister Chromatids are identical copies of a chromosome – made during DNA replication
o
The duplicated chromatids are initially attached along their lengths by protein complexes called
cohesins. This attachment is known as sister chromatid cohesion.
o
Each centromere is a specialized region of one
chromatid with specific DNA sequences.
✓
An unduplicated chromosome has a single centromere,
distinguished by the proteins that bind there, and two
arms.
The Cell Cycle:
Most cell division results in genetically identical daughter cells
12.1 Chromosomes are distributed during eukaryotic cell division
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Mitotic spindles are the fibers (microtubules) made during mitosis that pull sister chromatids apart.
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Centrosome is made up two centrioles and is the anchor for the mitotic spindles which are created.
(It is the central body from which the spindle originates)
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Centriole is a small set of microtubules that make up the centrosome which help to create
mitotic spindles for cell division.
The Cell Cycle:
Most cell division results in genetically identical daughter cells
12.1 Chromosomes are distributed during eukaryotic cell division
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Chromosomes (Homologous Chromosomes and Sister Chromatids)
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Centromeres
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Kinetochore
Mitotic Spindles
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Centrosome
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Centrioles
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
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The MITOTIC (M) PHASE of the cell cycle, which includes mitosis and cytokinesis, alternates with the
much longer INTERPHASE.
o Interphase accounts for about 90% of the cell cycle.
•
Interphase has three subphases: the G1 phase (“first
gap”), the S phase (“synthesis”), and the G2 phase
(“second gap”).
o
During all three subphases, a cell that will eventually
divide grows by producing proteins and cytoplasmic
organelles such as mitochondria and endoplasmic
reticulum.
o
Chromosomes are duplicated only during the S phase
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
A typical human cell might divide once every 24 hours.
o
Of this time, the M phase would last less than an hour and the S phase might take 10–12 hours, or
half the cycle.
o
The rest of the time would be divided between the G1 and G2 phases.
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
For convenience, MITOSIS is usually divided into five subphases: prophase, prometaphase, metaphase,
anaphase, and telophase.
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CYTOKINESIS, overlapping with the latter stages, completes the mitotic phase.
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
Following Cytokinesis, new daughter cells immediately enter Interphase (G1)
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In INTERPHASE (G1), the cell is not yet responding to signals to begin dividing
o
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During this phase, cells carry out their ‘normal’ operations
During INTERPHASE (S), the cell duplicates cellular organelles and structures
o Chromosomes are duplicated using DNA
Replication
o This forms two Sister Chromatids
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
In late INTERPHASE (G2), the chromosomes have been duplicated but are not condensed.
o
A nuclear membrane still exists.
o
The centrosome has replicated to form two centrosomes.
o
In animal cells, each centrosome features two centrioles
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
In PROPHASE, the chromosomes are tightly coiled, with sister chromatids joined together.
o
Chromosomes (Sister Chromatids) begin to condense
o
The mitotic spindle begins to form. It is composed of centrosomes and the microtubules that extend
from them.
o
The centrosomes move away from each other
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
During PROMETAPHASE, the nuclear envelope begins to break down
o
Spindle microtubules attach to the centromere region of sister chromatids
▪
A kinetochore (proteins within a centromere) is the actual site of attachment for spindle
microtubules
▪
The spindle begins to push sister chromatids towards the center of the cell
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
The spindle fibers push the sister chromatids until they are all arranged at the metaphase plate, an
imaginary plane equidistant from the poles, defining METAPHASE.
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
At ANAPHASE, the centromeres divide, separating the sister chromatids.
o
Each chromatid is pulled toward the pole to which it is attached by spindle fibers.
o
By the end, the two poles have equivalent collections of chromosomes.
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
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At TELOPHASE, daughter nuclei begin to form at the two poles.
o
Nuclear envelopes arise from the fragments of the parent cell’s nuclear envelope and other
portions of the endomembrane system.
o
The chromosomes become less tightly coiled and unpack.
o
The spindle begins to break down
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
•
CYTOKINESIS, division of the cytoplasm, is usually well under way by late telophase.
o
In animal cells, cytokinesis involves the formation of a cleavage furrow, which pinches the cell in
two.
o
In plant cells, vesicles derived from the Golgi apparatus produce a cell plate at the middle of the cell
The Cell Cycle:
The Key Roles of Cell Division
12.2 The mitotic phase alternates with interphase in the cell cycle
The Cell Cycle:
The mitotic phase alternates with interphase in the cell cycle
12.2 The mitotic spindle distributes chromosomes to daughter cells: a closer look
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The mitotic spindle, fibers composed of microtubules and associated proteins, is a major driving force in
mitosis.
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As the spindle assembles during prophase, the elements come from partial disassembly of the other
microtubules of the cytoskeleton.
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The spindle fibers elongate (polymerize) by incorporating more subunits of the protein tubulin and
shorten (depolymerize) by losing subunits
The Cell Cycle:
The mitotic spindle distributes chromosomes to daughter cells: a closer look
12.2 Cytokinesis divides the cytoplasm: a closer look
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Cytokinesis, division of the cytoplasm, typically follows mitosis.
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In animal cells, cytokinesis occurs by a process called cleavage
o The first sign of cleavage is the appearance of a cleavage furrow in the cell surface near the old
metaphase plate.
o On the cytoplasmic side of the cleavage furrow is a contractile ring of actin microfilaments
associated with molecules of the motor protein myosin.
✓ Contraction of the ring pinches the cell in two
The Cell Cycle:
REVIEW: Duplicate, Allocate, Separate
Interphase:
G1 – Follows cytokinesis; Normal cell operations; Cells signaled to divide
S – Organelles and chromosomes duplicated (Sister Chromatids)
G2 – Cell prepares to enter M Phase
M Phase:
Prophase – Chromosomes condense; Spindle forms; Centrosomes separate
Prometaphase – Spindle attaches to Sister Chromatids; Nuclear envelope breaks down
Metaphase – Spindle aligns sister chromatids at metaphase plate
Anaphase – Spindle separates sister chromatids
Telophase – Cleavage furrow forms; Nuclear envelope reforms; Spindle breaks down
Cytokinesis – Two identical daughter cells are created
The Cell Cycle:
REVIEW: Duplicate, Allocate, Separate
Interphase:
G1
S – DUPLICATE Chromosomes
G2
M Phase:
Prophase
Prometaphase
Metaphase
Anaphase – ALLOCATE Chromosomes
Telophase
Cytokinesis – SEPARATE into identical Daughter Cells
The Cell Cycle:
The Key Roles of Cell Division
12.3 The eukaryotic cell cycle is regulated by a molecular control system
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The timing and rate of cell division in different parts of an animal or plant are crucial for normal growth,
development, and maintenance.
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The frequency of cell division varies with cell type.
•
o
Some human cells divide frequently throughout life (skin cells).
o
Others human cells have the ability to divide but keep it in reserve (liver cells).
o
Mature nerve and muscle cells do not appear to divide at all after maturity.
Investigation of the molecular mechanisms regulating these differences provides important insights into
the operation of normal cells and may also explain how cancer cells escape controls
The Cell Cycle:
The eukaryotic cell cycle is regulated by a molecular control system
12.3 Cytoplasmic signals drive the cell cycle
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Fusion of an S phase cell and a G1 phase cell induces the G1 nucleus to start S phase
Additionally, Fusion of a cell in interphase (even G1 phase) with a cell in Mitosis induces the interphase
cell to enter mitosis
QUESTION: What does this evidence suggest regarding cell cycle control?
ANSWER: The cell cycle appears to be driven by specific chemical signals present in the cytoplasm.
The Cell Cycle:
The eukaryotic cell cycle is regulated by a molecular control system
12.3 Cytoplasmic signals drive the cell cycle
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The sequential events of the cell cycle are directed by a distinct cell cycle control system.
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Cyclically operating molecules trigger and coordinate key events in the cell cycle.
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A checkpoint in the cell cycle is a control point where stop and go-ahead signals regulate the cycle.
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The signals are transmitted within the cell by signal transduction
pathways.
The Cell Cycle:
The eukaryotic cell cycle is regulated by a molecular control system
12.3 Cytoplasmic signals drive the cell cycle
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The sequential events of the cell cycle are directed by a distinct cell cycle control system.
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Cyclically operating molecules trigger and coordinate key events in the cell cycle.
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A checkpoint in the cell cycle is a control point where stop and go-ahead signals regulate the cycle.
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The signals are transmitted within the cell by signal transduction
pathways.
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Animal cells generally have built-in stop signals that halt the cell cycle
at checkpoints until they are overridden by go-ahead signals.
Checkpoints also register signals from outside the cell
The Cell Cycle:
The eukaryotic cell cycle is regulated by a molecular control system
12.3 Cytoplasmic signals drive the cell cycle
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Three major checkpoints are found in the G1, G2, and M phases.
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For many cells, the G1 checkpoint, the “restriction point” in mammalian cells, is the most important.
o
If the cell receives a go-ahead signal at the G1 checkpoint, it
usually completes the cell cycle and divides.
The Cell Cycle:
The eukaryotic cell cycle is regulated by a molecular control system
12.3 Cytoplasmic signals drive the cell cycle
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If the cell does not receive a go-ahead signal, the cell exits the cycle and switches to a nondividing state,
the G0 phase
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So what is the difference between G1 and G0?
o
G1 is the ‘normal state’ for actively dividing cells
o
G0 is where most cells exist in the human body. This is
where quiescent cells reside that are not destined for cell
division
✓
Liver cells can be “called back” to the cell cycle by external
cues, such as growth factors released during injury.
✓
Highly specialized nerve and muscle cells never divide and
remain in a G0 state
The Cell Cycle:
Cytoplasmic signals drive the cell cycle
12.3 The cell cycle clock is regulated by cyclins and cyclin-dependent kinases
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Specialized control molecules pace the events of the cell cycle.
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These regulatory molecules are mainly proteins of two types: protein kinases and cyclins
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Protein kinases are enzymes that activate or inactivate other proteins by phosphorylating them.
o
Specific protein kinases give the go-ahead signals at the G1 and G2 checkpoints
o
The kinases that drive the cell cycle are present at constant concentrations but require the
association of a second protein, a cyclin, to become activated.
✓
Because of the requirement for binding of a cyclin, the kinases are called cyclin-dependent
kinases, or CDKs
✓
CDK’s carry out different functions in the cell cycle depending on which cyclin they are
associated with
The Cell Cycle:
Cytoplasmic signals drive the cell cycle
12.3 The cell cycle clock is regulated by cyclins and cyclin-dependent kinases
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Cyclins can activate CDK’s (specifically, CDK1)
o
When CDK-1 associates with Cyclins it is called MPF (Mitosis Promoting Factor)
o
G1-Cyclin associates with CDK1 to bypass the G1 Restriction Point
The Cell Cycle:
Cytoplasmic signals drive the cell cycle
12.3 The cell cycle clock is regulated by cyclins and cyclin-dependent kinases
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Cyclins activate CDK’s (specifically, CDK1)
o
When CDK-1 associates with Cyclins it is called MPF (Mitosis Promoting Factor)
o
G1-Cyclin associates with CDK1 to bypass the G1 Restriction Point
✓
o
In S-Phase, G1-Cyclin is broken down
Late in G2, M-Cyclin forms “Active MPF”, which allows the
cell to progress through the M-Phase
✓
The active MPF allows the cell to complete mitosis, but
also deactivates itself by breaking down M Cyclins
The Cell Cycle:
Cytoplasmic signals drive the cell cycle
12.3 The cell cycle clock is regulated by cyclins and cyclin-dependent kinases
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Because MPF breaks down M-Cyclins it deactivates itself before entering back into G1
o
The non-cyclin part of MPF, CDK1, persists in the cell until it associates with new cyclin molecules
synthesized during the G1 phase
QUESTION: What would happen if MPF didn’t break down
M-cyclins?
ANSWER: MPF would remain active and cells would
constantly overcome their G1 restriction and continually
divide
The Cell Cycle:
The cell cycle clock is regulated by cyclins and cyclin-dependent kinases
12.3 Internal and external cues help regulate the cell cycle
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The M phase checkpoint ensures that the kinetochores of all the chromosomes are properly attached to
the spindle at the metaphase plate before anaphase
This is not regulated by a cyclin-Cdk complex but an enzyme complex called separase
o
Separase cleaves the cohesins and allows the sister
chromatids to separate.
o
This block ensures that daughter cells do not end
up with missing or extra chromosomes.
o
QUESTION: What would happen if separase failed?
o
ANSWER: Sister Chromatids would never separate
and the cell would freeze in metaphase