Download Biology is the only subject in which multiplication is the same thing

Biology is the only subject in
which multiplication is the same
thing as division…
Chapter 11. How Cells Divide
The Cell Cycle:
Cell Growth, Cell Division
Where it all began…
 You started as a cell smaller than
a period at the end of a sentence…
.
And now look at you…
How did you
get from there
to here?
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
Getting the right stuff
 What is passed to daughter cells?

exact copy of genetic material = DNA
 this part of the cell cycle = mitosis

assortment of organelles & cytoplasm
 this part of the cell cycle = cytokinesis
chromosomes (stained orange)
in kangaroo rat epithelial cell
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

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
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
Chromosome
 Duplicated
chromosome
consists of
2 sister chromatids
narrow at their
centromeres
 contain identical
copies of the
chromosome’s
DNA

M
Mitosis
Cell cycle
 Cell has a “life cycle”
cell is formed from
a mitotic division
cell grows & matures
to divide again
G1, S, G2, M
epithelial cells,
blood cells,
stem cells
G2
Gap 2
G1
Gap 1
S
Synthesis
cell grows & matures
to never divide again
liver cells
G0
brain nerve cells
Muscle cells
G0
Resting
M
Mitosis
Cell Division cycle
 Phases of a dividing
G2
Gap 2
G1
Gap 1
cell’s life

interphase
S
Synthesis
 cell grows
 replicates chromosomes
 produces new organelles & biomolecules

mitotic phase
 cell separates & divides chromosomes
 mitosis

cytokinesis
 cell divides cytoplasm & organelles
G0
Resting
Interphase
 90% of cell life cycle

cell doing its “everyday job”
 produce RNA to synthesize proteins

prepares for duplication if triggered
 Characteristics


nucleus well-defined
DNA loosely
packed in long
chromatin fibers
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
Interphase G2
 Nucleus well-defined
chromosome duplication
complete
 DNA loosely packed in
long chromatin fibers

 Prepares for mitosis

produces proteins &
organelles
Mitosis
 copying cell’s DNA & dividing it
between 2 daughter nuclei
 Mitosis is divided into 4 phases
prophase
 metaphase
 anaphase
 telophase

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
Prometaphase
 Proteins attach to
centromeres

creating kinetochores
 Microtubules attach at
kinetochores

connect centromeres to
centrioles
 Chromosomes begin
moving
Kinetochore
 Each chromatid
has own
kinetochore
proteins

microtubules
attach to
kinetochore
proteins
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
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
Separation of chromatids
 In anaphase, proteins holding together
sister chromatids are inactivated

separate to become individual
chromosomes
1 chromosome
2 chromatids
2 chromosomes
Chromosome movement
 Kinetochores use
motor proteins that
“walk” chromosome
along attached
microtubule

microtubule
shortens by
dismantling at
kinetochore
(chromosome) end
Telophase
 Chromosomes arrive at
opposite poles
daughter nuclei form
 nucleoli form
 chromosomes disperse

 no longer visible under
light microscope
 Spindle fibers disperse
 Cytokinesis begins

cell division
Cytokinesis
 Animals
cleavage furrow forms
 ring of actin
microfilaments form
around equator of cell

 myosin proteins

tightens to form a
cleavage furrow, which
splits the cell in two
 like tightening a draw
string
Control of Cell Cycle
Overview
Cytokinesis in Animals
Mitosis in whitefish blastula
Mitosis in animal cells
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
Cytokinesis in plant cell
Mitosis in plant cell
onion root tip
Evolution of mitosis
 Mitosis in
eukaryotes likely
evolved from
binary fission in
bacteria
single circular
chromosome
 no membranebound organelles

Dinoflagellates
 algae
“red tide”
 Bioluminescence
 Development of
microtubules during
mitosis

Diatoms
 microscopic algae
marine
 Freshwater
 Development of
kinetochores

Evolution of
mitosis
 Mechanisms
intermediate
between
binary fission
& mitosis
seen in
modern
organisms

protists
Any Questions??
Regulation of Cell Division
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?
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
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
sister chromatids
There’s no
turning back,
now!
centromere
single-stranded
chromosomes
double-stranded
chromosomes
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

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?
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
G0 phase
 G0 phase
non-dividing, differentiated state
 most human cells in G0 phase

 liver cells
M
Mitosis
G2
Gap 2
S
Synthesis
 in G0, but can be
G1
Gap 1
G0
Resting
“called back” to cell
cycle by external cues
 nerve & muscle cells
 highly specialized;
arrested in G0 & can
never divide
Activation of cell division
 How do cells know when to divide?

cell communication = signals
 chemical signals in cytoplasm give cue
 signals usually mean proteins
 activators
 inhibitors
experimental evidence: Can you explain this?
“Go-ahead” signals
 Signals that promote cell growth &
division
proteins
 internal signals

 “promoting factors”

external signals
 “growth factors”
 Primary mechanism of control

kinase enzymes
Protein signals
 Promoting factors

Cyclins
 regulatory proteins
 levels of this cycle in the cell

Cdks
 cyclin-dependent kinases
 enzyme activates cellular proteins
 MPF
 maturation (mitosis) promoting factor

APC
 anaphase promoting complex
1970s-’80s | 2001
Cyclins & Cdks
 Interaction of Cdks & different Cyclins
triggers the stages of the cell cycle.
Leland H. Hartwell
checkpoints
Tim Hunt
Cdks
Sir Paul Nurse
cyclins
Spindle checkpoint
G2 / M checkpoint
Chromosomes
attached at
metaphase plate
• Replication
completed
• DNA integrity
Active
Inactive
Inactive
Cdk / G2
cyclin (MPF)
M
Active
APC
C
cytokinesis
mitosis
G2
G1
S
Cdk / G1
cyclin
Active
Inactive
G1 / S checkpoint • Growth factors
• Nutritional state of cell
• Size of cell
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)

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
Growth factor signals
Growth factor
Nuclear pore
Nuclear membrane
P
Cell surface
receptor
Protein kinase
cascade P
Cytoplasm
P
Cell division
Cdk
P
E2F
Chromosome
P
Nucleus
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
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
M
Mitosis
Cancer & Cell Growth
G2
Gap 2
 Cancer is essentially a failure
of cell division control

S
Synthesis
G1
Gap 1
G0
Resting
unrestrained, uncontrolled cell growth
 What control is lost?


p53 is the
Cell Cycle
Enforcer
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 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
by heat, radiation, or
chemicals.
Cell division stops, and
p53 triggers enzymes to
repair damaged region.
p53 triggers the destruction
of cells damaged beyond
repair.
ABNORMAL p53
Abnormal
p53 protein
Step 1
Step 2
DNA damage is
caused by heat,
radiation, or
chemicals.
The p53 protein fails to stop
cell division and repair DNA.
Cell divides without repair to
damaged DNA.
Cancer
cell
Step 3
Damaged cells continue to divide.
If other damage accumulates, the
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

escape apoptosis
 turn off suicide genes

immortality = unlimited divisions
 turn on chromosome maintenance genes

It’s like an
out of control
car!
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
chemical exposure
radiation exposure
heat




cigarette smoke
pollution
age
genetics
Tumors
 Mass of abnormal cells

http://www.hhmi.org/bioint
eractive/cancer/angiogene
sis.html
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
Traditional treatments for cancers
 Treatments target rapidly dividing cells

high-energy radiation &
chemotherapy with toxic drugs
 kill rapidly dividing cells
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
Any Questions??
Sexual reproduction lifecycle
 2 copies
 diploid
 2n
 1 copy
 haploid
 1n
fertilization
meiosis
We’re mixing
things up here!
A good thing?
 1 copy
 haploid
 1n
Meiosis
 Reduction Division



special cell division in
sexually reproducing
organisms
reduce 2n  1n
diploid  haploid
 “half”

makes gametes
 sperm, eggs
Warning: meiosis evolved from mitosis, so stages
& “machinery” are similar but the processes are
radically different. Do not confuse the two!
Overview of meiosis
I.P.M.A.T.P.M.A.T
2n=4
interphase 1
prophase 1
metaphase 1
anaphase 1
n=2
prophase 2 metaphase 2 anaphase 2 telophase 2
telophase 1
Double division
of meiosis
DNA replication
Repeat
I can’t
after
hear you!
me!
1st division of
meiosis separates
homologous pairs
Meiosis 1
Meiosis 2
2nd division of
meiosis separates
sister chromatids
Preparing for meiosis
 1st step of meiosis
Duplication of DNA
 Why bother?

 meiosis evolved after mitosis
2n = 6
single
stranded
 convenient to use
“machinery” of mitosis
 DNA replicated in
S phase of interphase
of MEIOSIS
(just like in mitosis)
M1 prophase
2n = 6
double
stranded
Meiosis 1
 1st division of meiosis
2n = 4
single
stranded
separates homologous pairs
prophase 1
2n = 4
double
stranded
metaphase 1
2n = 4
double
stranded
synapsis
tetrad
telophase 1
IRepeat
can’t
after
hear you!
me!
1n = 2
double
stranded
Meiosis 2
 2nd division of meiosis
1n = 2
double
stranded
separates sister
chromatids
prophase 2
What does
this division
look like?
1n = 2
single
stranded
1n = 2
double
stranded
metaphase 2
4
telophase 2
Steps of meiosis
 Meiosis 1
interphase
 prophase 1
 metaphase 1
 anaphase 1
 telophase 1

 Meiosis 2
prophase 2
 metaphase 2
 anaphase 2
 telophase 2

1st division of
meiosis separates
homologous pairs
(2n  1n)
“reduction division”
2nd division of
meiosis separates
sister chromatids
(1n  1n)
* just like mitosis *
Trading pieces of DNA
 Crossing over

during Prophase 1, sister
chromatids intertwine
 synapsis
 homologous pairs swap
pieces of chromosome
 DNA breaks & re-attaches
synapsis
tetrad
prophase 1
Crossing over
 3 steps
What are the
advantages of
sexual reproduction?
cross over
 breakage of DNA
 re-fusing of DNA

 New combinations of traits
Meiosis 1
Meiosis 2
“Let’s roll tape”
Meiosis square dance – find link!
http://www.youtube.com/watch?
v=iCL6d0OwKt8
Mitosis vs. Meiosis
Mitosis vs. Meiosis
 Mitosis






1 division
daughter cells
genetically identical
to parent cell
produces 2 cells
2n  2n
produces cells for
growth & repair
no crossing over
 Meiosis

2 divisions
daughter cells
genetically different
from parent
produces 4 cells
2n  1n
produces gametes

crossing over




Putting it all together…
meiosis  fertilization  mitosis + development
gametes
46
meiosis
23
23
egg
23
46
23
zygote
fertilization
sperm
46
46 46
46 46 46
46
46
46
mitosis
&
mitosis
development
The value of sexual reproduction
 Sexual reproduction introduces genetic variation

genetic recombination during meiosis
 independent assortment of chromosomes
 random alignment of homologous chromosomes in Meiosis 1

crossing over
 mixing of alleles across homologous chromosomes

random fertilization
 which sperm fertilizes which egg?
 Driving evolution

metaphase1
variation for natural selection
Variation from genetic recombination
 Independent assortment of chromosomes
meiosis introduces genetic variation
 gametes of offspring have different
combination of genes compared to the
gametes from their parents

 random assortment in humans produces
223 (8,388,608) different combinations in gametes
from Mom
from Dad
offspring
new gametes
made by offspring
Variation from crossing over
 Crossing over creates completely new
combinations of traits on each chromosome

creates an infinite
variety in gametes
Variation from random fertilization
 Sperm + Egg = ?

any 2 parents will produce a zygote with
over 70 trillion (223 x 223) possible diploid
combinations
Sexual reproduction creates variability
Sexual reproduction allows us to maintain both
genetic similarity & differences.
Michael & Kirk
Douglas
Chris & Liam
Hemsworth
Martin & Charlie Sheen, Emilio Estevez
Sperm production
Epididymis
Testis
Coiled
seminiferous
tubules
germ cell
(diploid)
primary
spermatocyte
(diploid)
MEIOSIS I
secondary
spermatocytes
(haploid)
Vas deferens
spermatids
(haploid)
spermatozoa
 Spermatogenesis


continuous
& prolific process
Cross-section of
seminiferous tubule
each ejaculation
=
100-600 million sperm
MEIOSIS II
Egg production
 Oogenesis
eggs in ovaries halted before
Anaphase 1, prior to birth
 Meiosis 1 completed during
maturation (in humans ~
once/month following
puberty)
 Meiosis 2 completed after
unequal division
fertilization
 1 egg + 2 polar bodies
Meiosis 1 completed
during egg maturation

ovulation
What is the advantage of
this development system?
Meiosis 2 completion
triggered by fertilization
Oogenesis
primary follicles
germinal cell
(diploid)
fallopian tube
fertilization
primary
oocyte
(diploid)
MEIOSIS I
secondary
oocyte
(haploid)
first polar body
MEIOSIS II
developing
follicle
mature follicle with
secondary oocyte
ruptured follicle
(ovulation)
after fertilization
second
polar body
ovum
(haploid)
corpus luteum
Differences across kingdoms
 Not all organisms use haploid & diploid
stages in same way


which one is dominant (2n or n) differs
but still alternate between haploid & diploid
 must for sexual reproduction
Any Questions??
What are the
DISadvantages of
sexual reproduction?