Cell Cycle

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Cell Cycle
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Identify the cell structures involved in cell
division.   Identify and explain the events that
occur in the stages of the cell cycle (G1, S, G2,
mitosis)   Explain the purpose of
mitosis.   Compare and contrast cytokinesis in
plant and animal cells.   Relate the role of
various factors on the mitotic process cell
checkpoints, density-dependent inhibition, growth
factors, cyclins and kinases.
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Why Cells Divide

• Why do cells need to divide?

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Cell Division - Purpose

• Provides a means of reproduction for organisms.
• Provides a means of growth in multicellular
  organisms.
• Provides a means of repair in multicellular
  organisms.

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Reproduction

• Unicellular organisms divide in order to form new
  organisms.

No Elizabeth, dont go!
Apologies to Gary Larson and the FAR SIDE
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Reproduction

• Multicellular organisms divide to reproduce
  special cells (gametes) that will carry out the
  formation of a new organism.

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Growth

• Multicellular organisms are made of millions to
  trillions of microscopic cells rather than a few
  large cells. Growth mainly occurs by increasing
  the number of cells.

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Repair

• Many microscopic cells as opposed to only a few
  large ones is also advantageous in the case of
  injury.
• How so?

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Is there any advantage to possessing many small
cells as opposed to a few large cells?
Examine the two cells below. The blue color
represents the area of diffusion of glucose
within the cell over equal periods of time. Do
you see a potential problem that might suggest an
answer to the question above?
nucleus
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Surface Area to Volume Ratio

• Relative size of the surface area of the plasma
  membrane and the volume of the cell reach a
  critical point.
• Analyze the
• following cubic cell

L W H
Day one 1 1 1
Day two 2 2 2
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Nuclear Limitations

• Limited capability of the nucleus
• -- there is a finite amount of genetic material
  because the genome size remains constant even as
  the cell grows.

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Why Cells Divide

• What actually triggers or cues the cell about the
  need to divide?

Most of it comes down to chemicals.
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Why Cells Divide

• Two irreversible points in cell cycle
• replication of genetic material
• separation of sister chromatids

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REPLICATION (S phase)
SEPARATION (anaphase)
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Why Cells Divide

• Checkpoints
• process is assessed possibly halted
• 3 major checkpoints
• G1/S
• can DNA synthesis begin?
• G2/M
• has DNA synthesis been
• completed correctly?
• commitment to mitosis
• spindle checkpoint
• are all chromosomes attached
• to spindle?
• can sister chromatids separate
• correctly?

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Checkpoint control system

• Checkpoints
• cell cycle controlled by STOP GO chemical
  signals at critical points
• signals indicate if key cellular processes have
  been completed correctly

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Why Cells Divide

• The decision to divide has both external and
  internal chemical influences.

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Why Cells Divide

• EXTERNAL
• Cells can have direct contact with each other
  through cell junctions or surfaces.
• Certain chemicals can easily come in contact with
  adjacent cells in this way.

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Why Cells Divide

• Cells can communicate with each other by
  secreting chemical messengers into the
  extracellular fluid.
• Paracrine signaling target is near the
  signaling source (ex. Adjacent cells)
• Hormonal signaling signal travels through
  bloodstream from source to target (pituitary
  ovaries)
• Synaptic signaling chemicals travel across
  small gap or synapse (neurotransmitters from
  neuron to neuron)

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Why Cells Divide

• The signaling process consists of 3 stages
• EXTERNAL
• Reception - Chemical messengers interact with
  receptors, often those of the plasma membrane.

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Why Cells Divide

• INTERNAL
• Transduction- This begins a chain of events in a
  chemical pathway within the cell, such as a
  phosphorylation cascade
• Phosphorylation cascading refers to the transfer
  of phosphate groups from one protein molecule to
  the next, via a type of kinase enzyme,
  subsequently activating the molecules in the
  pathway. (Think Domino effect)

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Why Cells Divide

• Response - cellular activity
• Could be
• Rearrangement of cytoskeleton
• Opening/closing ion channels
• Initiation of metabolic activity, such as cell
  division.

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Chemical Regulation of the Cell Cycle

• Once signaled, Kinase proteins give the go ahead
  signals at G1 and G2 checkpoints.
• Kinase proteins are a family of related proteins
  that activate proteins which in turn activate
  certain cell processes such as cell division.

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• These kinases (Cdks) themselves are not activated
  until they are attached to cyclin (becoming MPFs)
• Cyclin concentrations fluctuate within a cell,
  slowly building up until cell division begins.

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• The MPFs (Cdk-cyclin) cause nuclear membrane
  destruction and stimulate other kinases, setting
  the chain of events in motion known as mitosis.

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The Cell Cycle (Internet click here)(click on
the words above to go to website and ACQUIRE more
information on the cell cycle.)
The Cell Cycle (Internet click here)(click on
the words above to go to website and ACQUIRE more
information on the cell cycle.)

• Consists of phases characterized by important
  events in the life of a cell

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Cell Cycle

• Interphase
• G0 Most of your body cells are in this state.
  Non-dividing, differentiated and specialized for
  a specific job.
• G1- Essentially the same as G0,, however this
  phase is followed by phases leading to and
  including cell division.
• S Synthesis of chromosomes.
• G2- cell prepares for division more growth,
  production of extra organelles, proteins,
  membranes.
• M Mitosis Nuclear events Prophase,
  prometaphase, metaphase, anaphase, telophase
• Cytokinesis cytoplasmic division

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Spindle checkpoint
G2 / M checkpoint
Chromosomes attached at metaphase plate

• Replication completed
• DNA integrity

Inactive
Active
Active
Inactive
Cdk / G2cyclin (MPF)
M
cytokinesis
APC
C
mitosis
G2
G1
S
Cdk / G1cyclin
Inactive
MPF Mitosis Promoting Factor APC Anaphase
Promoting Complex
Active
G1 / S checkpoint

• Growth factors
• Nutritional state of cell
• Size of cell

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The Cell Cycle (Internet click here)and (click
here) (click on the words above to go to Cells
Alive! website and ACQUIRE more information on
the mitosis as needed.)

• Mitosis
• Prophase
• Metaphase
• Anaphase
• Telophase
• Sometimes these are divided further (prometaphase)

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After Mitosis

• MPFs (partially made of cyclin) levels must drop
  to allow the cell to enter interphase again.
• Proteins such as ubiquitin, regulate the cycle
  by causing the degradation of cyclin and kinases.
• This brings about the end of mitosis and the
  reforming of the nuclear membrane.
• Thus the new cells continue to interphase.
• Ubiquitin common across most eukaryotic
  species hence ubiquitous.

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Other Division Halting Processes

• Density-dependent inhibition
• when the cell density reaches a certain maximum,
  many cells stop dividing.
• Anchorage dependence contact with a substratum
  may influence if a cell stops dividing.

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External signals

• Growth factors
• coordination between cells
• protein signals released by body cells that
  stimulate other cells to divide
• density-dependent inhibition
• crowded cells stop dividing
• each cell binds a bit of growth factor
• not enough activator left to trigger division in
  any one cell
• Degradation of protein growth factors also
  possible
• anchorage dependence
• to divide cells must be attached to a substrate
• touch sensor receptors

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Example of a Growth Factor

• Platelet Derived Growth Factor (PDGF)
• made by platelets in blood clots
• binding of PDGF to cell receptors stimulates cell
  division in connective tissue
• heal wounds

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Other Division Halting Processes

• Necrosis and Apoptosis
• Necrosis death due to insult/injury
• Apoptosis programmed cell death
• What benefits would there be for an organism to
  destroy its own cells?
• http//virtuallaboratory.colorado.edu/Biofundament
  als/lectureNotes/Topic5-4_CellDeath.htm

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Cancer

• Transformation Alterations in genes implicated
  with cell cycle begin the conversion of a normal
  cell to cancerous cell.
• Oncogenes
• Tumor Supressor genes
• Tumor mass of abnormal cells
• Benign tumor remains at site
• Malignant Becomes invasive enough to interfere
  with organ function
• Metastasis cancer cells spread to other sites

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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
• turn off suicide genes
• immortality unlimited divisions
• turn on chromosome maintenance genes
• promotes blood vessel growth
• turn on blood vessel growth genes
• overcome anchor density dependence
• turn off touch-sensor gene

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p53 master regulator gene
NORMAL p53
p53 allows cells with repaired DNA to divide.
p53 protein
DNA repair enzyme
p53 protein
Step 2
Step 1
Step 3
DNA damage is caused by heat, radiation, or
chemicals.
p53 triggers the destruction of cells damaged
beyond repair.
Cell division stops, and p53 triggers enzymes to
repair damaged region.
ABNORMAL p53
abnormal p53 protein
cancer cell
Step 2
Step 1
Step 3
The p53 protein fails to stop cell division and
repair DNA. Cell divides without repair
to damaged DNA.
DNA damage is caused by heat, radiation, or
chemicals.
Damaged cells continue to divide. If other damage
accumulates, the cell can turn cancerous.
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Explain the purpose of meioisis.   Compare and
contrast the processes of mitosis and
meiosis. Distinguish between male and female
gametogenesis in humans.   Define tetrad,
homologous chromosome, synapsis.   Describe the
process of crossing-over.   Identify the
composition of a eukaryotic chromosome.   Explain
the results of a duplication, deletion, inversion
and translocation of chromosomes.   Define
nondisjunction and provide examples of several
genetic disorders resulting from nondisjunction.  
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Genomes and Chromosomes

• A Closer Look at Reproduction

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Genomes and Chromosomes

• An organism is determined by its organisms
  genetic material or genome.
• In order to maintain life, any new cells created
  must possess the same exact genome.

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Genome and Chromosomes

• The mitotic portion of the cell cycle ensures
  that the genome is transferred correctly to the
  new cells created.

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Genes and Chromosomes
Chromosomes are the condensed version of the
DNA-protein complex called chromatin.
http//images.sciencedaily.com/2009/10/09100511040
1-large.jpg
http//www.damours.iric.ca/Site/Projects_files/Chr
omatin_Nucleosomes.png
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Genes and Chromosomes

• Once the chromatin is replicated during the S
  phase of the cell cycle a cell is ready to divide.

Kinetochore
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Mitosis vs. Meiosis
Mitosis
Meiosis
Both
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Mitosis vs. Meiosis
Mitosis Both Meiosis
Chromosome Replication
Cell division end cell
Chromosome Result
During S phase
Once -two
Twice four
Same as original Diploid
Half of the original- haploid
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Meiosis

• For what purposes would HALF the chromosome
  material be appropriate?

For the union of two cells (gametes) sexual
reproduction.
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Meiosis I

• Homologous Chromosomes pair up forming a tetrad
  in a process called synapsis.
• At certain points the chromatids of the homologs
  may crisscross, forming a chiasmata.

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Meiosis I

• As the cell transists from metaphase to anaphase
  it is the homologs which are separated rather
  than the chromatids.

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Meiosis I

• Cytokinesis occurs, resulting in two haploid
  cells.
• Depending on the type of gamete, meiosis II may
  proceed directly or be carried out at a later
  date.

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Meiosis II

• Proceeds much like the process of mitosis,
  however, the end results differ due to Meiosis I.

4 haploid cells are created.
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Meiosis

• Humans
• Spermatogenesis 4 viable haploid sperm
  produced.
• Oogenesis 1 viable haploid egg and 3
  non-functional polar bodies produced.

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What is the advantage of producing one LARGE egg
as opposed to 4 smaller ones?
http//legacy.owensboro.kctcs.edu/gcaplan/anat2/no
tes/gametogenesis.jpg
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Meiosis

• Plants produce spores which then mitotically
  divide to form gametophyte. This produces gametes
  which then fuse to form sporophyte.

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Genetic Variation

• Does not exist in cells produced by mitosis,
  unless some mutation arises.
• Sexual reproduction provides a recombination of
  genetic material in 3 ways.

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Genetic Variation

• Independent assortment of homologues.

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Genetic Variation

• Random joining of gametes.

Getting here is only HALF the race Boys!
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Genetic Variation

• Crossing over,
• as demonstrated in lab activity,
• involves the exchange of genetic material
  between nonsister chromatids, during prophase I

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Genetic Variation

• Deletion and duplication
• see lab activity
• Inversion
• see lab activity

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CHROMOSOMES, KARYOTYPES, AND SEXUAL LIFE CYCLES
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KARYOTYPE
CARTOONIZED Ideogram of chromosome after
staining. The short arm of the chromosome is
referred to as p and the long arm as q.
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KARYOTYPE

• ORDERED DISPLAY OF AN INDIVIDUALS CHROMOSOMES.
• PREPARED BY TREATING CELLS WITH DRUG TO STIMULATE
  MITOSIS AND THEN ADDING ANOTHER TO STOP IT AT
  METAPHASE.

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KARYOTYPE

• CAN BE USED TO DIAGNOSE CERTAIN GENETIC DISORDERS
  (SUCH AS ANEUPLOIDY CAUSED BY NONDISJUNCTION).

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KARYOTYPES
COLOR ENHANCED BY COMPUTER
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KARYOTYPES

• BANDING CREATED BY THE USE OF DYES.
• USED TO IDENTIFY SPECIFIC CHROMOSOMES.

CHROMOSOME LENGTH, SHAPE, AND POSITION OF
CENTROMERE USED FOR IDENTIFICATION.
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KARYOTYPES
What can you determine about this individual?
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KARYOTYPES
What can you determine about this individual?
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KARYOTYPES
What about this individual?
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KARYOTYPES
LASTLY, WHAT ABOUT THIS INDIVIDUAL?
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Karyotypes

• The Biology Project click here, than choose
  karyotyping on the left side menu.

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GENOMIC IMPRINTING

• Some mammalian traits depend on which parent
  passed along the defective allele.
• Prader-Willi syndrome mental retardation,
  obesity (uncontrollable urge to eat), short
  stature. (father passes a partially deleted 15)
• Angelmann syndrome uncontrollable laughter,
  jerky movements, other motor/mental symptoms.
  (mother passes a partially deleted 15)

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Mitochondrial and Plastid DNA

• These organelles can reproduce themselves within
  a cell, passing along their own unique DNA to
  their offspring organelles.
• The DNA codes for some proteins specific to the
  organelles function.
• Which parent does YOUR mitochondrial DNA come
  from?

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Genes on the X chromosome

• As you know, genes on the X chromosome are said
  to be sex-linked.
• Several disorders, associated with sex-linkage,
  are recessive, such as hemophilia and
  colorblindness.

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Genes on the X chromosome

• Due to the pairing of the sex chromosomes, any
  recessive genes are more likely to be expressed
  in males then in females.
• However, because of X inactivation, resulting in
  Barr bodies, females can show signs of the
  recessive trait. (Mosaicism)

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Sexual Life Cycles

• Many organisms, other than animals, sexually
  reproduce.
• Sexual reproduction is a way to increase variety
  within a population.
• This can then lead to evolution of the
  populations themselves.
• The sexual life cycle itself, has been subject to
  evolutionary changes.

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