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CHAPTER 12
THE CELL CYCLE
What is the cell cycle?
• The cell cycle is a complex set of stages that is
highly regulated with checkpoints, which
determine the ultimate fate of the eukaryotic cell.
Heritable information provides for continuity of life.
• In eukaryotes, heritable information is passed to the
next generation via processes that include the cell
cycle and mitosis or meiosis plus fertilization.
1855 Rudolf Virchow
“Omnis cellula e cellula!”
• “Every cell originates from another cell.”
• From the observation that only certain
cells or groups of cells become sick.
• Doctor of anatomic pathology
(microscopes). Encouraged his students to
“think microscopically”
• 1st to recognize leukemia (cancer of the
blood or bone marrow)
Why do cells divide?
1. Continuity of life- reproduction. MITOSIS/MEIOSIS
2. Growth & Development (from single zygote).
MITOSIS
3. Renewal & repair (blood cells, skin cells) MITOSIS
•
•
•
•
•
surface:volume ratio (size)
genome:cytoplasmic ratio
hormones/growth factors
age… apoptosis
or don’t… because of contact inhibition
REPRODUCTION
Amoeba divides to form two cells
GROWTH & DEVELOPMENT
GROWTH & DEVELOPMENT
Sand dollar embryo shortly after fertilization… 1 -> 2 cells
TISSUE RENEWAL
Figure 12.1c The functions of cell division: Tissue renewal
bone marrow cells give rise
to blood cells.
What must happen before a cell
is ready to divide????
The cell must:
1. grow by producing proteins and
cytoplasmic organelles.
2. duplicate the DNA (chromosomes).
3. separate replicated chromosome(s) to
opposite sides of the cell.
CELL DIVISION
Prokaryotic
“Binary Fission”
vs.
Eukaryotic
Mitosis or Meiosis
PROKARYOTIC CELL DIVISION
• Bacterial genes are carried
on a single bacterial
chromosome (chromosome
is a loosely defined term).
• Shape = naked (no protein)
circular/ single loop- not
paired strands as in
eukaryotes.
• The origin of replication is
the first replicated region of
the DNA chromosomes.
Copies move apart rapidly
to opposite poles of the cell.
• Prokaryotes undergo binary
fission = “division in half”.
Eukaryotic Chromosomes
How are eukaryotic chromosomes different
from prokaryotic chromosomes?
1.
A Nucleus surrounds the EUK
chromosomes
2. A paired number of DNA
molecules- instead of one.
Characteristic # of chromosomes per
species.
Ex. Human 46, Dog 78, Amoeba 12, Cat
38, Chimp 48
3. Overall length of DNA- enormous
compared to prokaryotes. (human
DNA spans 3 meters)
4. DNA is packaged/condensed into
chromatin (DNA + PROTEIN) then
into nucleosomes then
chromosomes. (methylation)
a single chromosome is a long,
linear DNA molecule, containing
hundreds or thousands of genes.
chromatin is the DNA-histone
protein complex.
chromosomes assume the compact
shape prior to cell division.
Homologous Pairs of Chromosomes
• Homologous = same
• Chromosome pairs of the
same length containing the
same genes.
• One is inherited from the
organism’s father- the
other from the organism’s
mother during
fertilization.
• Good = back up copy of
each gene in case one is
mutated and nonfuntional.
REPLICATED DNA
• CHROMATIDS are
connected, identical
copies of the
chromosome’s DNA
molecule
• the CENTROMERE
is the narrow “waist”
of the duplicated
chromosome.
• portion of the
chromatids that is
“moved” during cell
division.
DIVISION OF THE CHROMOSOMES
WITHIN THE NUCLEUS
Mitosis = unicellular eukaryotes & multicell somatic cells
Mitosis passes a complete genome from the parent cell to
daughter cells.
makes identical diploid (chromosome pairs) cells
Ex. more muscle cells, more skin cells, more nerve cells
Meiosis = Germ cell division
Meiosis, a reduction division, followed by fertilization
ensures genetic diversity in sexually reproducing
organisms.
makes haploid (single chromosomes) sex cells
Ex. sperm or eggs
What is the difference between
mitosis/meiosis and cytokinesis?
• Mitosis/Meiosis is
nuclear divisionrefers to the separation
of replicated
chromosomes (DNA).
• Cytokinesis is division
of the cytoplasm once
2 new nuclei have
been established.
What is the cell
cycle?
INTERPHASE- 3 phases
• THE Cell
1. Grows
2. copies its DNA (synthesis)
3. prepares for nuclear
division (mitosis) .
• G1,S,G2
• 90% of the cycle
MITOSIS/MEIOSIS
nuclear divisionchromosome movement via
spindle fibers
CYTOKINESIS
cytoplasmic division
The cell cycle is directed by internal controls
or checkpoints. Internal and external signals
provide stop-and-go signs at the checkpoints.
Three “checkpoints”
Nondividing cells may exit the cell
Cycle (G0); or hold at a particular stage in
the cell cycle.
The most important checkpoint is G1.
A “stop” signal causes the cell to enter into
a stage where it no longer divides(G0).
Instead, it specializes and carries out the
programmed functions of that kind of cell.
Ex. manufacture protein or contract
Cells in (G0) can reenter the cell cycle
when given appropriate cues.
Ex. tissue damage or hormone signal
Regulation of the Cell Cycle
INTERNAL CONTROL by a distinct cell cycle control system
Which chemicals control the cell cycle?
• Protein kinases- enzymes that activate or
inactivate proteins by phosphorylating
them.
• Cyclin- Cyclins are proteins that fluctuate
in concentration in the cell- giving them
their name.
Activates a kinase by attaching to it.
• Cyclin-dependent Kinases (Cdks) are
inactive until cyclin binds to them.
MPF was the first cdk + cyclin complex discovered
“maturation-promoting factor”
Or “M-Phase-Promoting factor”
Gets the cell past the G2 checkpoint
So it is followed by nuclear division.
There are more examples of these
protein complexes that bind cyclin
to get the cell past all the regulatory
checkpoints.
Checkpoints:
G1, G2, and M
Figure 12.12 Evidence for cytoplasmic chemical signals in cell cycle regulation
Regulation of the Cell Cycle
EXTERNAL CONTROL by a distinct cell cycle control system
1.
Growth factor- protein
released by certain body
cells that stimulates
other cells to divide.
Ex. PDGF (platelet derived
growth factor)
2. Anchorage dependencecells must be attached to
a substratum like the
extra cellular matrix of
tissue.
3. Density-dependent
inhibition- crowded
cells stop dividing.
The effect of a growth factor on cell division
• What happens when cells produce an
excess amount of cyclin?
Cancer
• What is cancer?
Unregulated cell growth
and division.
• What causes cancer?
Damage to the genes
regulating the cell division
cycle.
– Usually by carcinogens.
• Cancer results from
disruptions in cell cycle
control
Winter break reading:
“The Immortal Life of
Henrietta Lacks”
By Rebecca Skloot
•
•
•
•
•
Tumor = a cluster of cancerous cells
Metastases = When cells leave the tumor, spread, grow new tumors.
Sarcomas = Tumors of the cells in connective tissue, muscle or bone.
Carcinoma = Tumors of cells in epithelial tissue like skin.
The three deadliest human cancers:
1. Lung …smoking
2. Colorectal …diet
3. Breast…causes is still unknown, however some forms are inherited as the
genes BRCA1 and BRCA 2.
Figure 12-17x2 Mammogram: normal (left) and cancerous (right)
• Genes that cause cancer are called oncogenes.
• The normal versions of these genes are called protooncogenes and they code for proteins that stimulate
normal cell growth and division.
• How do proto-oncogenes become oncogenes?
• Translocation, or movement of fragments of chromosomes (break off and attach
somewhere else) that result in being around an active promoter.
• Amplification, or increasing the number of copies of the gene in the cell.
• Point mutations, change the sequence, creating mutant proteins & VIRUSES!!!
• Two genes that are significant: ras gene and the p53
gene.
– The ras gene creates a protein that influences the cell cycle.
– The mutated ras protein is hyperactive, leading to excessive cell
division.
– The p53 gene becomes active when DNA is damaged and
creates a tumor suppressing protein.
– Mutating the p53 gene can lead to the formation of tumors.
– Chemicals in cigarette smoke induce p53 mutations.
• 15% of the cancers
worldwide are associated
with viral infections.
• Ex. Human Papilloma
Virus & Cervical Cancer
• Certain viruses can insert
oncogenes others may
insert DNA into protooncogenes, turning them
into oncogenes.
Figure 12.0 Mitosis
Cell division via mitosis involves the:1. replication,
2. alignment, & 3. separation of chromosomes.
Mitosis- replication, alignment,
separation of chromosomes
“IPMAT”
•
•
•
•
•
Interpase
Prophase
Metaphase
Anaphase
Telophase
•
•
•
•
•
I
Perceive
Many
Anxious
Teenagers
The names of the stages of mitosis are the same for meiosis…
Memorize them now…
Figure 12.5 The stages of mitotic cell division in an animal cell: G2 phase; prophase;
prometaphase
Figure 12.5 The stages of mitotic cell division in an animal cell: metaphase;
anaphase; telophase and cytokinesis.
Figure 12.5x Mitosis
Figure 12.9 Mitosis in a plant cell
INTERPHASE
• G1 phase “first gap”
growth by production of
proteins and cytoplasmic
organelles.
• S phase “synthesis”
DNA is replicated
• G2 phase “second gap”
cell growth by production of
proteins & organelles.
PROPHASE
• Nucleus & cytoplasmic
changes
• Chromatin fibers condense into
chromosomes
• visible “sister chromatids”
connected at centromere.
• Nucleoli dissapear.
• Nuclear envelope breaks down
• Centrosomes/ centrioles
migrate to opposite poles
METAPHASE
• Centrosomes are at
opposite poles
• Chromosomes line up in
the “middle” at the
metaphase plate
• Kinetochores (from
centromere) attached to
microtubules=spindle
fibers (from centrosomes)
• Whole thing called the
“mitotic spindle”
Figure 12.6 The mitotic spindle at metaphase
ANAPHASE
•
•
•
•
paired centromeres separate=
Sister chromatids separate
Each now = chromosome
Kinetochore microtubules
shorten @ end
• Each pole has equivalent and
complete collections of
chromosomes
Figure 12.7 Testing a hypothesis for chromosome migration during anaphase
TELOPHASE
• Non-kinetochore
microtubules elongate
the cell
• Daughter nuclei form
• Chromosomes become
less tightly coiled into
chromatin.
CYTOKINESIS
• Division of the
cytoplasm
• Cleavage furrow
(animals) pinches the
cell in two.
• Cell plate (plants)
formed as vesicles
deposit cell wall
materials to the middle
of the cell.
Figure 12.8 Cytokinesis in animal and plant cells
Figure 12-09x Mitosis in an onion root
1. When does mitosis occur?
2. What is the product of Mitosis followed by
cytokinesis?
3. Mitosis plays a role in what three activities of
life?
4. Mitosis is a continuous process with observable
structural features along the mitotic process.
What is the order of the processes?
(after DNA replication.)
(two genetically identical daughter cells.)
(growth, repair, and asexual reproduction)
(replication, alignment, separation).
The end.