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2005-2006 1
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Biology is the only subject in
which multiplication is the same
thing as division…
AP Biology 2005-2006
Chapter 12.
The Cell Cycle:
Cell Growth, Cell Division
AP Biology 2005-2006
Getting from there to here…
Cell division
continuity of life =
reproduction of cells
reproduction
unicellular organisms
growth
repair & renew
Cell cycle
life of a cell from
origin to division into
2 new daughter cells AP Biology 2005-2006
Getting the right stuff
What is passed to daughter cells?
exact copy of genetic material = DNA
this division step = mitosis
assortment of organelles & cytoplasm
this division step = cytokinesis
chromosomes (stained orange)
in kangaroo rat epithelial cell
AP Biology 2005-2006
Copying DNA
Dividing cell duplicates DNA
separates each copy to
opposite ends of cell
splits into 2 daughter cells
human cell duplicates ~3 meters DNA
separates 2 copies so each daughter cell
has complete identical copy
error rate = ~1 per 100 million bases
3 billion base pairs
mammalian genome
~30 errors per cell cycle
mutations AP Biology 2005-2006
A bit about DNA
DNA is organized in
chromosomes
double helix DNA molecule
associated proteins =
histone proteins
DNA-protein complex =
chromatin
organized into long
thin fiber
2005-2006 2
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Copying DNA with care…
After DNA duplication chromatin condenses
coiling & folding to make a smaller package
from DNA to chromatin to highly condensed
mitotic chromosome
AP Biology 2005-2006
Chromosome
Duplicated
chromosome
consists of
2 sister chromatids
narrow at their
centromeres
contain identical
copies of the
chromosome’s
DNA
AP Biology 2005-2006
Cell cycle
M
Mitosis
G1
Gap 1
G0
Resting
G2
Gap 2
S
Synthesis
Cell has a “life cycle”
cell is formed from
a mitotic division
cell grows & matures
to divide again
cell grows & matures
to never divide again
G1, S, G2, M G0
epithelial cells,
blood cells,
stem cells
brain nerve cells
AP Biology 2005-2006
Cell Division cycle
M
Mitosis
G1
Gap 1
G0
Resting
G2
Gap 2
S
Synthesis
Phases of a dividing cell’s life
interphase
cell grows
replicates chromosomes
produces new organelles & biomolecules
mitotic phase
cell separates & divides chromosomes mitosis
cell divides cytoplasm & organelles cytokinesis
AP Biology 2005-2006
Control of Cell Cycle
AP Biology 2005-2006
Interphase 90% of cell life cycle
cell doing its “everyday job”
produce RNA, synthesize proteins
prepares for duplication if triggered
Characteristics
nucleus well-defined
DNA loosely
packed in long
chromatin fibers
2005-2006 3
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Interphase
Divided into 3 phases:
G1 = 1st Gap
cell doing its “everyday job”
cell grows
S = DNA Synthesis
copies chromosomes
G2 = 2nd Gap
prepares for division
cell grows
produces organelles, proteins, membranes
AP Biology 2005-2006
Interphase G2
Nucleus well-defined
chromosome duplication
complete
DNA loosely packed in
long chromatin fibers
Prepares for mitosis
produces proteins &
organelles
AP Biology 2005-2006
Mitosis
copying cell’s DNA & dividing it
between 2 daughter nuclei
Mitosis is divided into 4 phases
prophase
metaphase
anaphase
telophase
AP Biology 2005-2006
Overview
AP Biology 2005-2006
Prophase Chromatin (DNA) condenses
visible as chromosomes
chromatids
fibers extend from the
centromeres
Centrioles move to opposite
poles of cell
Fibers (microtubules) cross cell
to form mitotic spindle
actin, myosin
Nucleolus disappears
Nuclear membrane breaks down
AP Biology 2005-2006
Prometaphase
Proteins attach to
centromeres
creating kinetochores
Microtubules attach at
kinetochores
connect centromeres to
centrioles
Chromosomes begin
moving
2005-2006 4
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Kinetochore
Each chromatid
has own
kinetochore
proteins
microtubules
attach to
kinetochore
proteins
AP Biology 2005-2006
Metaphase
Spindle fibers align chromosomes along the middle of cell
meta = middle
metaphase plate
helps to ensure chromosomes separate properly so each new nucleus
receives only 1 copy of each chromosome
AP Biology 2005-2006 AP Biology 2005-2006
Anaphase
Sister chromatids separate at kinetochores
move to opposite poles
pulled at centromeres
pulled by motor proteins “walking”along microtubules
increased production of ATP by mitochondria
Poles move farther apart
polar microtubules lengthen
AP Biology 2005-2006
Separation of chromatids
In anaphase, proteins holding together
sister chromatids are inactivated
separate to become individual
chromosomes
2 chromosomes 1 chromosome
2 chromatids AP Biology 2005-2006
Kinetochores use
motor proteins that
“walk” chromosome
along attached
microtubule
microtubule
shortens by
dismantling at
kinetochore
(chromosome) end
Chromosome movement
2005-2006 5
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Telophase
Chromosomes arrive at opposite poles
daughter nuclei form
nucleoli from
chromosomes disperse
no longer visible under light microscope
Spindle fibers disperse
Cytokinesis begins
cell division
AP Biology 2005-2006
Cytokinesis
Animals
cleavage furrow forms
ring of actin
microfilaments forms
around equator of cell
myosin proteins
tightens to form a
cleavage furrow, which
splits the cell in two
like tightening a draw
string
AP Biology 2005-2006
Cytokinesis in Animals
(play Cells Alive movie here)
AP Biology 2005-2006
Mitosis in whitefish blastula
AP Biology 2005-2006
Mitosis in animal cells
AP Biology 2005-2006
Cytokinesis in Plants
Plants
vesicles move to equator line up & fuse to form 2 membranes = cell plate
derived from Golgi
new cell wall is laid down between membranes
new cell wall fuses with existing cell wall
2005-2006 6
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Cytokinesis in plant cell
AP Biology 2005-2006
Mitosis in plant cell
AP Biology 2005-2006
onion root tip
AP Biology 2005-2006
Evolution of mitosis
Mitosis in
eukaryotes likely
evolved from
binary fission in
bacteria
single circular
chromosome
no membrane-
bound organelles
AP Biology 2005-2006
Evolution of
mitosis
Mechanisms
intermediate
between
binary fission
& mitosis
seen in
modern
organisms
protists
AP Biology 2005-2006
Chapter 12.
Regulation of Cell Division
2005-2006 7
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Coordination of cell division
Multicellular organism
need to coordinate across different
parts of organism
timing of cell division
rates of cell division
crucial for normal growth, development
& maintenance
do all cells have same cell cycle?
Why is this such a hot topic right now? AP Biology 2005-2006
Frequency of cell division
Frequency of cell division varies with
cell type
skin cells divide frequently throughout life
liver cells retain ability to divide, but keep it in reserve
mature nerve cells & muscle cells
do not divide at all after maturity
AP Biology 2005-2006
Cell Cycle Control
Two irreversible points in cell cycle
replication of genetic material
separation of sister chromatids
Cell can be put on hold at specific
checkpoints
centromere
sister chromatids
single-stranded chromosomes
double-stranded chromosomes
AP Biology 2005-2006
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
AP Biology 2005-2006
Checkpoint control system
3 major checkpoints:
G1
can DNA synthesis begin?
G2
has DNA synthesis been
completed correctly?
commitment to mitosis
M phases
spindle checkpoint
can sister chromatids
separate correctly? AP Biology 2005-2006
G1 checkpoint
G1 checkpoint is most critical
primary decision point
“restriction point”
if cell receives “go” signal, it divides
if does not receive “go” signal,
cell exits cycle &
switches to G0 phase
non-dividing state
2005-2006 8
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
G0 phase
M
Mitosis
G1
Gap 1
G0
Resting
G2
Gap 2
S
Synthesis
G0 phase
non-dividing, differentiated state
most human cells in G0 phase
liver cells
in G0, but can be
“called back” to cell
cycle by external cues
nerve & muscle cells
highly specialized;
arrested in G0 & can
never divide AP Biology 2005-2006
How do cells know when to divide?
cell communication = signals
chemical signals in cytoplasm give cue
signals usually mean proteins
activators
inhibitors
Activation of cell division
experimental evidence: Can you explain this?
AP Biology 2005-2006
“Go-ahead” signals
Signals that promote cell growth &
division
proteins
internal signals
“promoting factors”
external signals
“growth factors”
Primary mechanism of control
phosphorylation
kinase enzymes
AP Biology 2005-2006
Protein signals
Promoting factors
Cyclins
regulatory proteins
levels cycle in the cell
Cdks
cyclin-dependent kinases
enzyme activates cellular proteins
MPF maturation (mitosis) promoting factor
APC
anaphase promoting complex
AP Biology 2005-2006
Cyclins & Cdks Interaction of Cdks & different Cyclins
triggers the stages of the cell cycle.
AP Biology 2005-2006
Chromosomes attached at metaphase plate
• Replication completed • DNA integrity
• Growth factors • Nutritional state of cell • Size of cell
Cdk / G1
cyclin
Cdk / G2
cyclin (MPF)
G2
S
G1
C M
Spindle checkpoint G2 / M checkpoint
G1 / S checkpoint
APC
Active Inactive
Active Inactive
Inactive
Active
mitosis
cytokinesis
2005-2006 9
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Cyclin & Cyclin dependent kinases CDKs & cyclin drive cell from one phase to next in
cell cycle
proper regulation of cell
cycle is so key to life
that the genes for these
regulatory proteins
have been highly
conserved through
evolution
the genes are basically
the same in yeast,
insects, plants &
animals (including
humans)
AP Biology 2005-2006
External signals
Growth factors
external signals
protein signals released by body cells that stimulate other cells to divide
density-dependent inhibition crowded cells stop dividing
mass of cells use up growth factors
not enough left to trigger cell division
anchorage dependence to divide cells must be attached
to a substrate
AP Biology 2005-2006
E2F
Nucleus Cytoplasm
Cell division
Nuclear membrane
Growth factor
Protein kinase cascade
Nuclear pore
Chromosome
Cdk Cell surface receptor
P
P P
P
P
Growth factor signals
AP Biology 2005-2006
Example of a Growth Factor
Platelet Derived Growth Factor (PDGF)
made by platelets (blood cells)
binding of PDGF to cell receptors stimulates
fibroblast (connective tissue) cell division
wound repair
growth of
fibroblast cells
(connective
tissue cells)
helps heal
wounds
AP Biology 2005-2006
Growth Factors and Cancer
Growth factors influence cell cycle
proto-oncogenes
normal genes that become oncogenes
(cancer-causing) when mutated
stimulates cell growth
if switched on can cause cancer
example: RAS (activates cyclins)
tumor-suppressor genes
inhibits cell division
if switched off can cause cancer
example: p53 AP Biology 2005-2006
M
Mitosis
G1
Gap 1
G0
Resting
G2
Gap 2
S
Synthesis
Cancer & Cell Growth
Cancer is essentially a failure
of cell division control
unrestrained, uncontrolled cell growth
What control is lost?
checkpoint stops
gene p53 plays a key role in G1 checkpoint
p53 protein halts cell division if it detects damaged DNA
stimulates repair enzymes to fix DNA
forces cell into G0 resting stage
keeps cell in G1 arrest
causes apoptosis of damaged cell
ALL cancers have to shut down p53 activity
p53 is the Cell Cycle Enforcer
p53 discovered at Stony Brook by Dr. Arnold Levine
2005-2006 10
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
DNA damage is caused by heat, radiation, or chemicals.
p53 allows cells with repaired DNA to divide.
Step 1
DNA damage is caused by heat, radiation, or chemicals.
Step 1 Step 2
Damaged cells continue to divide. If other damage accumulates, the cell can turn cancerous.
Step 3 p53 triggers the destruction of cells damaged beyond repair.
ABNORMAL p53
NORMAL p53
Abnormal p53 protein
Cancer cell
Step 3 The p53 protein fails to stop cell division and repair DNA. Cell divides without repair to damaged DNA.
Cell division stops, and p53 triggers enzymes to repair damaged region.
Step 2
DNA repair enzyme p53
protein p53
protein
p53 — master regulator gene
AP Biology 2005-2006
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
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 censor gene
It’s like an out of control
car!
AP Biology 2005-2006
What causes these “hits”?
Mutations in cells can be triggered by
UV radiation
chemical exposure
radiation exposure
heat
cigarette smoke
pollution
age
genetics
AP Biology 2005-2006
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 tumors
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
AP Biology 2005-2006
Traditional treatments for cancers
Treatments target rapidly dividing cells
high-energy radiation & chemotherapy with toxic drugs
kill rapidly dividing cells
AP Biology 2005-2006
New “miracle drugs”
Drugs targeting proteins (enzymes)
found only in tumor cells
Gleevec
treatment for adult leukemia (CML)
& stomach cancer (GIST)
1st successful targeted drug
2005-2006 11
Division Ave. High School Ms. Foglia
AP Biology
AP Biology 2005-2006
Any Questions??