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Cell

Divisio
n
Mitosis &
Meiosis

Image: Cell Division, Wikipedia From the Virtual Cell Biology Classroom on ScienceProfOnline.com
• Who has a bigger cell? Elephant or
Mouse?
• Why do cells divide instead of just growing
bigger?
– The larger the cell, the more demands it
places on DNA
• Small cells, the DNA can meet the needs of the
cell
• As cell grows, the DNA can not meet the needs of
the cell – does not make extra copies of DNA to
meet needs
Frequency of cell division
• Frequency of cell division varies by cell type
– embryo
• cell cycle < 20 minute
– skin cells
• divide frequently throughout life
• 12-24 hours cycle
– liver cells
• retain ability to divide, but keep it in reserve M
• divide once every year or two metaphase anaphase
prophase telophase
– mature nerve cells & muscle cells G2
C

• do not divide at all after maturity


• permanently in G0 interphase (G1, S, G2 phases)
mitosis (M)
cytokinesis (C) G1
S
Eukaryotic Cell Cycle
Like prokaryotic cell cycle, in that…

– Cell grows.

– DNA is replicated.

- Mitotic cell division produces daughter


cell identical to the parent.

Different from prokaryotic


cell cycle, in that…
– Eukaryotic cells have more DNA on many linear chromosomes.
(Q: How many do humans have?).

– The timing of replication and cell division is highly regulated.

Image: Cell cycle by Richard Wheeler From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Eukaryotic Cell Cycle

2 major phases:

• __________ (3 stages)
– DNA uncondensed

• ________ (4 stages + cytokinesis)


- Nuclear division & division of cytoplasm
– DNA condensed

Image: Cell cycle by Richard Wheeler From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Interphase
Non-dividing state
With 3 sub-stages:
___ – cell grows in size
– organelles replicated

___ – replication of DNA


– synthesis of proteins
associated with DNA

___ – synthesis of proteins


associated with mitosis

Image: Cell cycle by Richard Wheeler; Interphase in


Onion Cell Drawing & Photo, Source Unknown From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Cycle Phases
• G1 – First growth phase. Metabolic activity
proceeds at a normal rate. Duration highly
variable. Synthesis of enzymes related to DNA
replication.
• G0 – Quiescent (rest) state. Usually for non-
proliferative cells. Can occur for cells that are
damaged. Alternative to apoptosis. Can be
temporary or permanent.
• Nerve and muscle cells (multinucleated)
• S – DNA replication.
– All chromosomes replicated.
– Chromosomes consist of 2 sister chromatids in
chromatin form.
– Histones produced.
Chromosome
• 1 long string of DNA Sister chromatids

• Loose- chromatin
• Tight - chromatid
Fig. 12-4
0.5 µm Chromosomes DNA molecules

Chromo-
Chromosome
some arm
duplication
(including DNA
synthesis)
Centromere

Sister
chromatids

Separation of
sister chromatids

Centromere

Sister chromatids
• G2
– Second growth phase.
– Reproduction of some organelles. High microtubule
production.
– Two centrosomes. Aster around each centrosome.
Cells grow in size.
• M – Mitosis.
– Prophase, Prometaphase, Metaphase, Anaphase,
Telophase
• Cytokinesis
– Birth of 2 daughter cells
Checkpoints
• The cell cycle is regulated by a molecular
signaling system which switches the cell
cycle control system on/off.
• The system consists of a molecular clock
and checkpoints to ensure conditions are
met before moving on to the next steps.
• Malfunctions may lead to cancer.
Fig. 12-14
G1 checkpoint

Control
system S
G1

M G2

M checkpoint
G2 checkpoint
Mitosis
Division of somatic cells (non-reproductive cells)
in eukaryotic organisms.

A single cell divides into two identical


daughter cells.

Daughter cells have same # of chromosomes


as does parent cell.

Images: Cell cycle by Richard Wheeler;


Overview of Mitosis, Mysid From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Mitosis
4 sub-phases:
1st – Prophase

2nd – Metaphase

3rd – Anaphase

4th – Telophase

followed by

Cytokinesis

Secret to remembering phases in order…

Image: Mitosis diagram, Marek Kultys From the Virtual Cell Biology Classroom on ScienceProfOnline.com
1. Prophase

3 Major Events

- chromosomes condense

- spindle fibers form


(spindle fibers are specialized microtubules
radiating out from centrioles)

- chromosomes are
captured by spindle
Fluoresced eukaryotic cell.
Chromosomes in blue. Mitotic spindle
apparatus in green.

Images: Prophase drawing, Henry Gray's Anatomy of the Human Body;


Prophase Onion Cell Drawing & Photo, Source Unknown, Fluoresced cell,
National Institutes of Health
From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Prophase
chromatin condensing
nucleus
chromosomes
nucleolus

centrioles
2. Metaphase
• chromosomes align along
equator of the cell, with one
kinetochore facing each pole

centrioles
chromosomes

spindle fibers
Kinetocores not pictured in this illustration.

Images: Metaphase drawing, Henry Gray's Anatomy of the Human


Body; Metaphase Onion Cell Drawing & Photo, Source Unknown
3. Anaphase

• sister chromatids separate

• spindle fibers attached to


kinetochores shorten and
pull chromatids towards the
poles.

• free spindle fibers lengthen


and push poles of cell apart

Images: Anaphase drawing, Henry Gray's Anatomy of the Human


Body; Anaphase Onion Cell Drawing & Photo, Source Unknown From the Virtual Cell Biology Classroom on ScienceProfOnline.com
4. Telophase
• spindle fibers disintegrate

• nuclear envelopes form around both


groups of chromosomes

•chromosomes revert to their


extended state

• cytokinesis occurs, enclosing each


daughter nucleus into a separate cell

Images: Telophase drawing, Henry Gray's Anatomy of the Human


Body; Telophase Onion Cell Drawing & Photo, Source Unknown From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Cytokinesis – Plant vs. Animal Cell

• Plant cells undergo


cytokinesis by forming a
cell plate between the two
daughter nuclei.

• Animal cells undergo


cytokinesis through the
formation of a cleavage
furrow. A ring of
microtubules contract,
pinching the cell in half.

Images: Telophase drawing, Henry Gray's Anatomy of the Human Body;


Ciliate dividing, TheAlphaWolf; Telophase Onion Cell Photo, Source Unknown From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Stages of Mitosis

REVIEW!
Mitosis Animations
1. Mitosis & Cytokinesis from McGraw-Hill
2. Mitosis Interactive Animation from Cells Alive

Image: Onion Cell Drawing & Photo, Source Unknown


Genetics Terminology
SEXually reproducing eukaryotes, have 2 types of body cells…

Made
you
look!

1. somatic cells

2. sex cells
(a.k.a. gametes)

Image: Superficial human anatomy, Mikael Häggström&


Rainer Zenz; Sperm & egg, Wikipedia From the Virtual Cell Biology Classroom on ScienceProfOnline.com
What is cell division of gametes called?

Meiosis
- A single germ cell divides into four unique daughter cells.

- Daughter cells have half the # of chromosomes as parent cell,


so they considered haploid.

Image: Overview of Meiosis,


National Institutes of Health From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Genetics Terminology: Ploidy
Refers to the number of sets of
chromosomes in cells.

● Haploid – one copy of each chromosome


– designated as “n”, the number of
chromosomes in one “set”
- gametes

● Diploid – two sets of chromosomes


- two of each chromosome
– designated as “2n”
- somatic cells

Diploid organisms receive one of each type of


chromosome from female parent (maternal chromosomes)
and one of each type of chromosome from male
parent (paternal chromosomes)

From the Virtual Cell Biology Classroom on ScienceProfOnline.com


Genetics Terminology: Homologues

Chromosomes exist in homologous pairs in diploid (2n)


cells.

Exception: Sex chromosomes (X, Y).

Other chromosomes, known as autosomes, they have


homologues.

From the Virtual Cell Biology Classroom on ScienceProfOnline.com


Karyotype
• Q: Which, of the top
two karyotypes is
replicated?

• Q: How many
homologous pair in each
karyotype?

• Q: How is the bottom


karyotype different
from the top two?

From the Virtual Cell Biology Classroom on ScienceProfOnline.com Image: Karyotype, National Human Genome Research Institute
Asexual Reproduction
– Many single-celled
organisms reproduce by
splitting, budding.

– Some multicellular
organisms can reproduce
asexually, produce clones
(offspring genetically identical
to parent).

– Q: What type of cell


division is asexual
reproduction?

Image: Paatrick Star, Nickelodeon;


From the Virtual Cell Biology Classroom on ScienceProfOnline.com Hydra budding, Lifetrance;
Sexual Reproduction

• Fusion of two gametes to


produce a single zygote.

• Introduces greater genetic


variation, allows genetic
recombination.

• With exception of self-


fertilizing organisms, zygote
has gametes from two
different parents.

Peter + Lois = Stewie

Images: Peter, Lois & Stewie, The Family Guy From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Sexual reproduction in humans …
• At fertilization, 23 chromosomes
are donated by each parent.
(total = 46 or 23 pairs).

• Gametes (sperm/ova):
– Contain 22 autosomes and 1 sex
chromosome.
– Are haploid (haploid number
“n” = 23 in humans).

• Fertilization results in diploid zygote.


– Diploid cell; 2n = 46. (n = 23 in humans)

• Q: Most cells in the body are produced through what type of cell division?

• Only gametes are produced through meiosis.

Image: Superficial human anatomy, Mikael


Häggström& Rainer Zenz; Sperm & egg, Wikipedia From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Meiosis - Sex Cell (Gamete) Formation

In meiosis, there
are 2 divisions
of the nucleus:

meiosis I
&
meiosis II

Image: Overview of Meiosis,


National Institutes of Health From the Virtual Cell Biology Classroom on ScienceProfOnline.com
REVIEW!
Meiosis Animations
1. How Meiosis Works from McGraw-Hill
2. Meiosis Interactive Animation from Cells Alive

From the Virtual Cell Biology Classroom on ScienceProfOnline.com Image: Meiosis diagram, Marek Kultys
Meiosis & Sexual Reproduction
Life Cycle

Mitosis * *
*

From the Virtual Cell Biology Classroom on ScienceProfOnline.com Image: Animal Life Cycle, Dr. T’s Bio 328 Genetics
Genetic Variation in Diploid Organisms

• Fusion of sperm and egg results in unique


offspring.

• But not only because the young are a product of


two individuals with different genetic makeup.

• Meiosis “shuffles” the genes so that the an


individual’s gametes are genetically different
from one another.

How is this shuffling accomplished?

From the Virtual Cell Biology Classroom on ScienceProfOnline.com Image: Meiosis diagram, Marek Kultys
Genetic shuffling of Meiosis I
In addition to a new combination of chromosomes resulting
from fertilization, there are also events in Meiosis I that
shuffle the genes.

1. Crossing over in Prophase I.

2. Independent assortment in Metaphase I.

From the Virtual Cell Biology Classroom on ScienceProfOnline.com


Crossing Over
• Homologues break at identical
locations, then rejoin opposite
partners.

• This creates new combinations


of the alleles on each
chromosome.

• Occurs randomly several times


on every chromosome.

• Results in mixing of the genes


you inherited from your
parents.

Image: Meiosis diagram, Marek Kultys ; Crossing over, Thomas


From the Virtual Cell Biology Classroom on ScienceProfOnline.com Hunt Morgan, Molecular crossing over, David Hall
Independent Assortment

REVIEW!
Independent Assortment Animations
1. Independent Assortment from Sinauer Associates
2. Random Orientation of Chromosomes During Meiosis from McGraw-Hill
Males produce sperm
throughout life, after Spermatogenesis
the onset of puberty,
about 1,500 sperm per
second.

From the Virtual Cell Biology Classroom on ScienceProfOnline.com Image: Spermatogenesis, Wiki
Oogenesis
Oogenesis in females is
probably complete
either before or
shortly after birth.

During oogenesis, three


polar bodies develop as
the mature ovum is
generated.

Polar bodies contain


little cytoplasm and
eventually degenerate.

From the Virtual Cell Biology Classroom on ScienceProfOnline.com Image: Oogenesis, Wiki
Mitosis vs. Meiosis
• 1n
• 2n
• Daughter cells different from
• Clone
parent cell and from each other.
• Same genetic
• Daughter cells have ½ the
information in
number of chromosomes as
parent cell and
somatic cell.
daughter cell.
• Shuffling the genes
• Give me another (Mix it up!)
one just like the
other one!

From the Virtual Cell Biology Classroom on ScienceProfOnline.com


Image: Mitosis diagram & Meiosis diagram, Marek Kultys From the Virtual Cell Biology Classroom on ScienceProfOnline.com
Quality Control
• Systems for interrupting the cell cycle if
something goes wrong
1) DNA damage checkpoint
1) happens at G1 checkpoint + S phase + M phase
2) P53 gene – tumor suppresor
2) Completion of S-phase
1) Makes sure that there are no okazaki fragments
3) Spindle Checkpoint
1) Assures spindles are properly connected to
kinetichore
• If problem cannot be fixed, the cell signals for
apoptosis
Cancer
• A group of diseases that involve irregular growth
and reproduction of cells
• Cancer occurs when genes involved in the cycle,
specifically with check points are altered (growth
factors)
• Transformation – single cell converts to a cancer
cell
• Benign Tumor – a group of abnormal cells that
does not invade other body systems- not
considered cancerous
• Metastasis – when cancerous cells break
off the original tumor and travel to other
parts of the body
• Malignant Tumor – a tumor that invades a
body system by traveling via the
bloodstream or the lymphatic system
• Cancer causes death b/c the cells take
over the function of organs
• Cancer arises due to damage to genes
(90%) or inheritance (10)
Fig. 12-20

Lymph
vessel
Tumor
Blood
vessel

Cancer
Glandular
cell
tissue Metastatic
tumor
1 A tumor grows 2 Cancer cells 3 Cancer cells spread 4 Cancer cells may
from a single invade neigh- to other parts of survive and
cancer cell. boring tissue. the body. establish a new
tumor in another
part of the body.
Growth Factors and Cancer
• Growth factors can create cancers
– proto-oncogenes
• normally activates cell division
– growth factor genes
– become Oncogenes (cancer-causing) when mutated
• if switched “ON” can cause cancer
• example: RAS (activates cyclins)
– Tumor Suppressor Genes
• normally inhibits cell division
• if switched “OFF” can cause cancer. Why?
• example: p53
Cancer & Cell Growth
• Cancer is essentially a failure
of cell division control
– unrestrained, uncontrolled cell growth
• What control is lost?
– lose checkpoint stops
– gene p53 plays a key role in G1/S restriction point
• p53 protein halts cell division if it detects damaged DNA
p53 is the – options:
Cell Cycle » stimulates repair enzymes to fix DNA
Enforcer » forces cell into G0 resting stage
» keeps cell in G1 arrest
» causes apoptosis of damaged cell
• ALL cancers have to shut down p53 activity
• Inhibits blood vessel growth in tumors (angiogenesis)
p53 discovered at Stony Brook by Dr. Arnold Levine
p53 — master regulator gene
NORMAL p53
p53 allows cells
with repaired
DNA to divide.
p53
protein DNA repair enzyme
p53
protein

Step 1 Step 2 Step 3


DNA damage is caused Cell division stops, and p53 triggers the destruction
by heat, radiation, or p53 triggers enzymes to of cells damaged beyond repair.
chemicals. repair damaged region.

ABNORMAL p53

abnormal
p53 protein

cancer
Step 1 Step 2 cell
The p53 protein fails to stop
DNA damage is
caused by heat, cell division and repair DNA. Step 3
Damaged cells continue to divide.
radiation, or Cell divides without repair to If other damage accumulates, the
chemicals. damaged DNA. cell can turn cancerous.
Development of Cancer
• Cancer develops only after a cell experiences ~6
key mutations (“hits”)
– unlimited growth
• turn on growth promoter genes
– ignore checkpoints
• turn off tumor suppressor genes (p53)
– escape apoptosis
It’s like an
• turn off suicide genes
out-of-control
– immortality = unlimited divisions
car with many
• turn on chromosome maintenance genes
systems failing!
– promotes blood vessel growth
• turn on blood vessel growth genes
– overcome anchor & density dependence
• turn off touch-sensor gene
What causes these “hits”?
• Mutations in cells can be triggered by
 UV radiation  cigarette smoke
 chemical exposure  pollution
 radiation exposure  age
 heat  genetics
Tumors
• Mass of abnormal cells
– Benign tumor
• abnormal cells remain at original site as a lump
– p53 has halted cell divisions
• most do not cause serious problems &
can be removed by surgery
– Malignant tumor
• cells leave original site
– lose attachment to nearby cells
– carried by blood & lymph system to other tissues
– start more tumors = metastasis
• impair functions of organs throughout body

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