Chapter 11

• Parents cells produce a new generation of cells or multicelled individuals like themselves
• Parents must provide daughter cells with hereditary instructions, encoded in
DNA, and enough metabolic machinery to start up their own operation

Cells must either reproduce or they die.
Cells that can not reproduce and are destined to die are terminal cells (red blood, nerve cells, muscles cells etc.).
The "life of a cell" is termed the cell cycle as there are distinct phases.

Eukaryotic organisms
– Mitosis
– Meiosis
Prokaryotic organisms
– Prokaryotic fission

• Multicelled organisms
– Growth
– Cell replacement; Replace dead/worn out cells, repair damaged tisues.
– Produces diploid (2N) cells. Maintains species chromosome number
• Some protistans, fungi, plants, animals
– Asexual reproduction

• A DNA molecule & attached proteins
• Duplicated in preparation for mitosis
• Called sister chromatids.
one chromosome (unduplicated) one chromosome (duplicated)

• Sum total of chromosomes in a cell
• Somatic cells (body cells)
– Chromosome number is diploid (2 n )
– Two of each type of chromosome
• Gametes (sex cells)
– Chromosome number is haploid ( n )
– One of each chromosome type

• Diploid chromosome number ( n ) = 46
• Two sets of 23 chromosomes each (23 pairs)
– One set from father
– One set from mother
• Mitosis produces cells with 46 chromosomes-two of each type (diploid)

DNA and proteins arranged as cylindrical fiber
DNA one nucleosome histone
Figure 9.2
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This graph represents the amount of DNA found in the cell during the cell cycle
A –G1
B- S
C- G2
D- Mitosis

2 parts - interphase (growth) and mitosis (division) interphase
G1
S
Mitosis telophase anaphase metaphase prophase
G2
Figure 9.4
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• Usually longest part of the cycle (90%)
• Cell increases in mass
• Number of cytoplasmic components doubles
• DNA is duplicated
• 3 phases
– G1- gap 1, most of the carbohydrates, lipids, and proteins for a cell's own use and for export are assembled (nutrients).. growth. Organelles double
– S- synthesis, phase, the cell copies its DNA and synthesizes proteins used in organizing the condensed chromosomes (histones).
– In G2 – gap 2, the proteins that will drive mitosis to completion are produced

•
During interphase, chromosomes are not visible but are “relaxed” or uncoiled.
This is called chromatin and allows for protein synthesis and DNA replication. A human has over 6 feet of DNA prior to S.
Each daughter cell needs a copy of the
DNA found in the mother cell. To prevent DNA breakage, chromosomes are formed in prophase of mitosis.

• Period of nuclear division (karyokinesis)
• Usually followed by cytoplasmic division
• Four stages:
Prophase
Metaphase
Anaphase
Telophase

Prophase (Prepare)
Metaphase (Chromomes Middle)
Anaphase (Chromosomes Apart)
Telophase (Chrom. Totally separate)

Prophase (prepare): Mitosis Begins
1. Chromosomes become visible as rodlike units, each consisting of two sister chromatids. (they coil)
2. In the cytoplasm, the microtubules of the cytoskeleton break apart and begin reassembling
(make spindles and polar fibers) .
3. The nuclear envelope begins to disintegrate.
4. The centrioles (2-pairs), which have duplicated by the time prophase is underway, are now moved by the microtubules to the opposite poles of the cell
5. nucleolus breaks down

Early prophase – Centrioles begin to move apart. Chromosomes appear as long thin threads. Nucleolus become less distinct.
Middle prophase – Centrioles farther apart, asters begin to form. Twin chromatids become visible.

• New microtubules are assembled
• One centriole pair is moved toward opposite pole of spindle
• Nuclear envelope starts to break up
Figure 9.7
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Centrioles nearly reach opposite sides of nucleus. Spindle begins to form and kinetochore microtubules project from centromeres toward spindle poles. Nuclear membrane is disappearing. Nucleolus is no longer visable.

• Consists of two distinct sets of microtubules
– Each set extends from one of the cell poles
– Two sets overlap at spindle equator
• Moves chromosomes during mitosis
• Asters part of the spindle apparatus

• Spindle forms
• Spindle microtubules become attached to the two sister chromatids of each chromosome
• Spindle fibers “grab” onto the chromatids at the centromere
(kinetochore)
Figure 9.7
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• All chromosomes are lined up at the spindle equator
• Chromosomes are maximally condensed
Figure 9.7
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Metaphase-Nuclear membrane has disappeared.
Kineteocore microtubules move each twinchromatid chromosome to the equator. Other spindle microtubules interact with spindle tubules from opposite poles.

• Sister chromatids of each chromosome are pulled apart
• Once separated, each chromatid is a chromosome
• Sister chromatids separate and move toward opposite poles.
– Microtubules attached to the centromeres shorten and pull the chromosomes toward the poles.
– centromere divide
• Polar fibers lengthen pushing the poles apart
– microtubules at the spindle poles ratchet past each other to push the two spindle poles apart.
Figure 9.7
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Early anaphase – centromeres have split and begun moving toward opposite poles of spindle.
Spindle microtubules from opposite poles pull the poles apart.
Late anaphase – Two set of single chromasomes are nearing poles. Cytokinesis begins.

• Begins when the chromosomes of each original chromatid pair arrive at opposite poles.
• Chromosomes decondense.
Chromosomes return to the threadlike form typical of interphase. (uncoil, chromatin)
• Two nuclear membranes form, one around each set of unduplicated chromosomes
Figure 9.7
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• Usually occurs between late anaphase and end of telophase
• Two mechanisms
– Cell plate formation (plants)
– Cleavage (animals)

Figure 9.8
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1. Because of the rather rigid cell wall, the cytoplasm of plant cells cannot just be pinched in two.
2. Instead vesicles packed with wall building materials fuse with one another and the remnants of the microtubular spindle form a disklike structure. Then cellulose deposits during cell plate formation.

Figure 9.9
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1. The flexible plasma membrane of animal cells can be squeezed in the middle to separate the two daughter cells –a process called cleavage.
2. microfilaments pull the membrane inward until there are 2 daughter cells
3. the cleavage furrow – the indentation in the membrane

• Two daughter cells
• Each with same chromosome number as parent cell
• Chromosomes in unduplicated form
Figure 9.7
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Mitosis without cytokinesis results in coencytic bodies without individual cells.
Happens in some plants, fungi, algae and even a few animals. Animals cells do cytokinesis by the pinching in of the cell membrane.

Prokaryotic cells must reproduce quickly and can do so in about 20 minutes. The
DNA in a prokaryote is a circular chromosome that does not have histone DNA.
Replication occurs in a process called binary fission not mitosis. The circular chromosome attaches to the plasma membrane and then replicates the DNA. Only one replica-tion fork moving in opposite directions is formed. Afterward the plama membrane and new cell wall pinches in for cytokinesis.

• Different types of cells go through the cell cycle at different rate
• Once S begins, the cycle automatically runs through G2 and mitosis
• The cycle has a built-in molecular brake in G1
• Cancer involves a loss of control over the cycle, malfunction of the “brakes”

• Some cells normally stop in interphase (never progress any further)
– Neurons in human brain
– Arrested cells do not divide
• Adverse conditions can stop cycle
– Nutrient-deprived amoebas get stuck in interphase

• The phases are triggered by the accumulation of control substances called cyclins.
• The cell division cyclins interact with molecules called kinases. Kinases are proteins that phosphorylate other chemical messengers or enzymes that trigger the cell cycle phases.

-The cell division kinase or cyclin dependent kinase (cdk) has the ability to activate a cellular messenger for either DNA replication or mitosis. The messengers are called cyclins. Mcyclin for mitosis and the S-cyclin for DNA synthesis

Mitosis is complete and the CDK kinase is inactive.

As G1 progresses, the cell makes the
S-cyclin protein.
The level of cyclins fluctuates while the level of kinases remains rather constant.

The S-cyclin protein binds to the CDK kinase. When this happens the CDK kinase takes on the
DNA promoting form.

The chemical messenger attaches to the CDK protein. Once a threshold is reached the chemical messenger is phosphorylated. It leaves the CDK kinase and signals the start of
DNA replication.

Once the chemical messenger leaves, the Scyclin protein is destroyed. The
CDK kinase goes back to its inactive form.

Toward the end of S, the cell begins to make M-cyclin protein, which attaches to the CDK kinase. The CDK kinase now takes on the mitosis promoting form. The complex is called the
MPF or "maturationpromoting factor"

Now the chemical messenger can attach to the CDK kinase and be phosphorylated. At a threshold, it will be released. The chemical messenger will trigger mitosis. Once the chemical messenger leaves, the M-cyclin protein is destroyed. The CDK kinase returns to its inactive form and the process will reset itself.

Various cyclins are made and destroyed throughout the cell cycle whereas the level of cell division kinases remain constant. Kinases however are activated by various cyclins and the activity are mirrored by the rise and fall of cyclins.

Fluctuations in concentration of cyclins allow for cell cycle checkpoints. The three major check points are found in
G1, G2 and M phases. These check points have build-in-stop signals that hold the cell cycle at the checkpoint until overridden by go-ahead signals.

Often the G1 check point or "restriction point" in mammalian cells seems to be the most important one. If a cell receives a go-ahead signal at this check-point, it will complete the cell cycle and divide. However, if the cell does not receive the go-ahead signal in
G1, the switches to a nondividing state called G0.

How CDKs actually work is not well understood but the CDKs seem to activate other proteins and enzymes that affect particular steps in the cycle. There has been several discoveries-

Internal Signal-
To move past the M-phase checkpoint, an anaphase-promoting-complex APC must be activated. In order for this complex to be activated, all the kinetichore must be attached to spindle fibers. Unattached kinetichores release a signal that keeps the
APC in an inactive state so that anaphase does not begin. This ensures that each daughter cell is not missing any chromosomes.

External Signals-This include certain chemical and physical factors that affect cell division. Mammalian cells need certain nutrients and regulatory proteins or growth factors are needed for cell division. For example, when the skin has been damage (wound), platelets release a substance called platelet-derived growth factor (PDGF). This growth factor stimulate fibroblast cells to start to reproduce and make scar tissue.

External signals can effect how cells grow in culture.
Density-dependent inhibition- cells in culture stop dividing when they become crowded forming a single layer of cells. It seems that when crowded, there is insufficient growth factor produced and nutrients for cell division to continue.

Anchorage dependence- mammalian cells need to be attached to substratum like the inside of a culture jar or other tissue in order to reproduce.
This phenomenon is linked to a control system attached to the plama membrane proteins and the cytoskeleton. These phenomen keep the growth of tissue in check.
Cancer cells do not exhibit density-dependent inhibition or anchorage dependence.