Chapter 12: The Cell Cycle

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Cell Division & Cell Cycle
• http://www.youtube.com/watch?v=Q6ucKWII
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Chapter 12: The Cell Cycle
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Omnis cellula e cellula
From every cell a cell – Rudolf Virchow
• Cell division: reproduction of cells
• Cell cycle: life of a cell from the time it is first
formed from a dividing parent cell until it
divides into 2 daughter cells
• Mitosis: nuclear division within a cell, followed
by cytokinesis
• Cytokinesis: division of the cytoplasm
– It is crucial that genetic material remains the same
from generation to generation
Mitosis
• Mitosis functions in
– Reproduction of single-celled organisms
– Growth
– Repair
– Regeneration
• In contrast, meiosis produces gametes in
sexually-reproducing organisms
– Contains half the number of chromosomes of a
somatic cell
Organization of the Genetic Material
• Cell division results in genetically
identical daughter cells
– This requires DNA replication
followed by division of the nucleus
• Genome: genetic content of the
cell
– Prokaryotic cells have circular DNA
Circular DNA: a single long molecule
– Eukaryotic cells contain a number of
DNA molecules specific to different
species
One eukaryotic cell has about 2
meters of DNA
The DNA molecules in a cell are packaged into
chromosomes
– Eukaryotic chromosomes consist of chromatin, a complex of
DNA and protein that condenses during cell division
– Euchromatin: less condensed and readily available for
transcription
– Heterochromatin: highly compacted during interphase and
therefore not transcribed
• Somatic cells: include all body cells, aside from
reproductive cells
• Gametes: reproductive cells, include sperm and egg
Distribution of Chromosomes During Cell Division
• Non-dividing cells contain chromatin
– In human cells there are 46 strands of chromatin,
or 23 corresponding pairs of strands
• Dividing cells contain chromosomes
– Chromosomes becomes condensed prior to
mitosis
– Chomrosomes contain sister chromatids bound
by a centromere
• Centromere contains kinetochore
• Kinetochore: a structure of proteins associated with
specific sections of chromosomal DNA at the
centromere
Chromosome Structure
0.5 µm
A eukaryotic cell has multiple
chromosomes, one of which is
represented here. Before
duplication, each chromosome
has a single DNA molecule.
Chromosome
duplication
(including DNA
synthesis)
Once duplicated, a chromosome
consists of two sister chromatids
connected at the centromere. Each
chromatid contains a copy of the
DNA molecule.
Mechanical processes separate
the sister chromatids into two
chromosomes and distribute
them to two daughter cells.
Figure 12.4
Centromere
Separation
of sister
chromatids
Centromeres
Sister
chromatids
Sister chromatids
Mitotic Phase Alternates with Interphase in Cell
Cycle
• Mitosis: M Phase includes
mitosis and cytokinesis
–
–
–
–
–
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
• Interphase: 90% of cell
cycle; cell grows,
producing organelles and
proteins
– G1: First gap
– S: Synthesis, chromosome
replication
– G2: Second gap; completes
preparation for cell
division
INTERPHASE
G1
S
(DNA synthesis)
G2
In 24 hours…
• Mitosis: 1 hour
• G1: 5-6 hours (most variable)
• S: 10-12 hours
INTERPHASE
• G2: 4-6 hours
G1
S
(DNA synthesis)
G2
Mitotic Spindle is Necessary for Nuclear Division
Aster
Centrosome
• Mitotic spindle: used to
segregate sister
chromatids in anaphase
• Consists of microtubules
Overlapping
and proteins
nonkinetochore
microtubules
• Microtubules are able to
Kinetochores microtubules
Microtubules
change in length
Sister
chromatids
Metaphase
Plate
Kinetochores
0.5 µm
Chromosomes
– Elongate by adding
Tubulin subunits
– Shorten by loss of
Tubulin subunits
Centrosome
1 µm
Mitotic Spindle
• Interphase: the centrosome is
replicated and the two centrosomes
remain paired near the nucleus
– Centrosome or Microtubule
Organizing Center (MTOC): contains
two centrioles
• Prophase: spindle formation
• Early Prophase: migration of
centrosomes to poles, spindle
microtubules grow
• Late Prophase: centrosomes are at
the poles, asters form
– Aster: radial array of short
microtubules
– The mitotic spindle includes the
centrosomes, spindle microtubules
and asters
Mitotic Spindle
Prometaphase:
• Kinetochore: protein structure
assiciated with specific
sections of the chromosomal
DNA at the centromere
• Kinetochore microtubules:
attach kinetochore to spindle
• Metaphase Plate: created as
microtubules attach to
kinetochore, creation
indicates Metaphase starts
Cellular Changes Indicate
M- Phase Initiation
G2 of Interphase: nuclear
envelope intact
– Nucleus and nucleolus
present
– Centrosome Replication
• Animal cells contain
centrioles
– Chromosomes are not
condensed and
therefore not
individually visible
Prophase
• Nucleoli disappear
• Chromosomes condense
• Sister chromatids form
– Two genetically identical
arms joined by the
centromere and cohesin
proteins
– Mitotic spindle forms
using microtubules;
asters form
– Centrosome migration as
microtubules lengthen
Prometaphase
• Nuclear envelope
fragments and
microtubules invade
nuclear area
• Nonkinetochore
microtubules elongate
• Chromosomes condense
further and gain
kinetochore proteins
• Spindle fibers
(microtubules) interact
with kinetochores
Metaphase
• Longest stage of mitosis
– Can last up to 20 minutes
• Metaphase plate: site of
chormosome alignment
• Centrosomes are at poles
• Sister chromatid
kinetochores attach to
kinetochore microtubules
Anaphase
• Shortest stage of mitosis
• Cohesins between sister
chromatids are cleaved by enzymes
– Sister chromatids are now separate
chromosomes
• Spindle fibers shorten causing
chromosomes to move to opposite
poles
– Spindles shorten at kinetochore ends
according to Borisy et al.
– Evidenced by Tubulin break down
near fluorescently-labeled
kinetochores in pig kidney cells
• Nonkinetochore microtubules
elongate cell
Telophase
• Daughter nuclei form in cell
• Chromosomes loosen and
become less dense
• Nucleoli reappear
Cytokinesis
• Occurs in animal cells only
• Relies on cleavage marked by a
cleavage currow
• Cytoplasmic side of cleavage
furrow contains actin
microfilaments and myosin
– As the actin and myosin interact
the ring contracts and the
cleavage furrow deepens
Cellular Division in Plant Cells
• Plant cells form a cell plate following mitosis
• Golgi vesicles contain cell wall materials and
migrate toward the center of the cell – forming
the cell plate
Binary Fission
• Asexual eukaryotes
can utilize mitosis
for reproductive
purposes – this is
called binary
fission
• Asexual
prokaryotes
perform binary
fission that does
not involve mitosis
Evolution of Mitosis
• Some proteins were
highly conserved
• In prokaryotes, protein
resembling eukaryotic
actin may help with cell
division
– Tubulin-Like proteins may
help separate daughter
cells
Attach to nuclear
envelope
Reinforce spatial
arrangement of
nucleus
Spindle inside
nucleus
Cell Cycle
Regulation
•Cytoplasmic regulators as
shown in Mammalian cell
Fusion experiment by
Johnson and Rao (1970)
Cell Cycle Control System
• Control systems vary cell to
cell
– Skin cells divide frequently,
liver cells only divide when
needed (after injury), and
nerve and muscle cells never
divide
• Cytoplasmic molecules signal
cell cycle as shown by
Johnson and Rao
• Cell cycle events are
regulated cyclicly
– These are referred to as Cell
Cycle Checkpoints
Cell Cycle Control Systems
• Cell Cycle Checkpoint: control
point in cell cycle where stop
and go-ahead signals can
regulate the cycle; relies on
signal transduction pathways
controlled by internal and
external molecular signals
– G1 checkpoint: acts as a
mammalian restriction point
• “Go Signal” permits G1, S, G2 and M
• “Stop signal” causes G0 phase: nondividing state, state of most human
cells
– G2 checkpoint
– M checkpoint
Cell Cycle Clock
• The rate of cell cycle is
controlled by two
proteins:
– Cyclins
– Cyclin-dependent
kinases (Cdks)
Cell Cycle Clock
• Kinases: activate or inactivate other proteins
via phosphorylation
– Inactive most of the time
– Kinases are activated by cyclins
• Cyclins: regulatory proteins that have a cyclic
(fluctuating) concentration in the cell
• Cyclin-dependent kinases (Cdks)
– Activity fluctuates with cyclin concentration
Cell Cycle Clock
• MPF: maturationpromoting factor or Mphase promoting factor
– MPF is a Cyclin-Cdk
complex
• Triggers cell passage from
G2 to M
• G2 checkpoint: As cyclin
builds during G2 it binds
with Cdk
– Resulting MPF
phosphorylates proteins,
initiating Mitosis
• During anaphase, MPF inhibits itself by
destroying its own cyclin
– Cdk persists in the cell
Stop and Go Signals
• Internal signals
– M Phase checkpoint relies on kinetochore
signaling
– Allows for enzymatic cleavage of cohesins
• External factors
– Nutrients
– Growth Factor Dependency
– Density-dependent inhibition
– Anchorage dependence
External Factors
• Growth Factor Dependency:
over 50 known
– Platelet-derived Growth Factor
(PDGF): made by platelets,
required for fibroblast division in
culture, used at injury sites in
animals
– Fibroblasts have PDGF receptors
• PDGF receptors are receptor
tyrosine kinases
• Density-Dependent Inhibition:
corwded cells stop dividing
– Cell surface protein binds the
adjoining cell sends a growthinhibiting signal to cells
• Anchorage Dependence: cells
require a growth substratum
Cancer Cells
• Lack response to cell signals
– Some can divide indefinitely (ex: HeLa cervical
cancer cells)
– Cancer cells are not density or anchorage
dependent
• Cancer starts with transformation
– Normal cell becomes cancerous; this occurs
regularly and is usually amended by the immune
system
– If not, the cancer cell divides and becomes a
tumor
Cancer Cells
• Benign tumors: can be removed by surgery
• Malignant tumors: invade surrounding tissues and organs,
and often metastasize
– Metastasis: spread of cancer to far locations in the body
• Treatment options
– Radiation: destroys cancer cells
– Chemotherapy: medication that targets rapidly dividing cells
(including cancer cells)
• Ex: Taxol – stops dividing cells by prevents microtubule depolymerization in
metaphase, but also affects cells that naturally divide often such as
intestinal cells and skin cells of hair follicles
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