Cell Cycle

Activities of a cell from one cell

division to the next
Why do cells divide?
Growth
Development
Repair
Reproduction



Essential Features of Cell Division
1. Transmit a complete copy of
genetic information (DNA)
2. Transmit materials necessary for
cell to survive and use genetic information
3
Daughter
Cells
DNA Copied
Cells
Mature
Cells prepare for
Division
Cell Divides into
Identical cells
G1 - To cycle or not to cycle
S- Replicating the genome
M-Segregating the genome
Cytokinesis - Making two cells
1
st
growth stage after cell division

Cells mature by making more cytoplasm &
organelles

Cell carries on its normal metabolic
activities

Cell increases in size

Cell prepares to copy its DNA

5
Synthesis stage
DNA is copied or replicated

6
Two
identical
copies
of DNA
Original
DNA
Duplicated
chromosomes
are called
chromatids &
are held
together by the
centromere

7
Called Sister Chromatids
Duplication of Chromosome
2n
2n
2n
2
nd
Growth Stage
Occurs after DNA has been
copied
All cell structures needed for
division are made (e.g.
centrioles)
Both organelles & proteins are
synthesized
9
Cell growth and protein
production stop
Cells energy used to make 2
daughter cells
Called mitosis or karyokinesis
(nuclear division)
11
Mitosis Meiosis
Number of
divisions
1
2

Number of
daughter cells
2 4
Genetically
identical?
Yes No
Chromosome # Same as parent Half of parent
Where Somatic cells Germ cells
When Throughout life At sexual maturity
Role
Growth and
repair
Sexual reproduction
12
Division of the
nucleus
Also called
karyokinesis
Only occurs in
eukaryotes
Has four stages
Doesnt occur in
some cells such
as brain cells
13
1. Prophase
2. Metaphase
3.Anaphase








4.Telophase
Prophase
i) chromosomes condense
3 major events
ii) spindle fibers form
iii) chromosomes are captured by
spindle
Mitotic Spindle Forms
spindle fibers are specialized
microtubules
spindle fibers radiate out from
centrioles, forming the aster
centrioles occur in pairs, and are
duplicated during interphase
one pair of centrioles migrates to
one pole of cell, the other pair
migrates to opposite pole of cell
17
Kinetochore Fiber
Chromosome
Spindle Captures Chromosomes
When spindle fibers are fully formed
nuclear envelope disintegrates and
nucleolus disappears
Spindle fibers attach to chromosomes at
the kinetochore, a structure located at
the centromere
function of spindle fibers is to organize
division of sister chromatids into daughter
cells
20
Chromosomes, attached to the
kinetochore fibers, move to the center
of the cell
Chromosomes are now lined up at the
equator
21
Pole of
the Cell
Equator of Cell
22
Aster
Chromosomes at Equator
Spindle
Fibers
Animal Cell
Plant Cell
24
Occurs rapidly
Cell chromosomes are
separated
Spindle fibers shorten
so chromosomes
pulled to ends of cell
Animal cell

Plant cell


Photographs from:
http://www.bioweb.uncc.edu/biol1110/Stages.htm
26
Sister chromatids at
opposite poles
Spindle disassembles
Nuclear envelope forms around
each set of sister chromatids
Nucleolus reappears
CYTOKINESIS occurs
Chromosomes reappear as
chromatin

Animal Cell
Plant Cell
Means division of the cytoplasm
Division of cell into two,
identical halves called daughter
cells
In plant cells, cell plate forms
at the equator to divide cell
In animal cells, cleavage furrow
forms to split cell
28
29
Cleavage furrow
in animal cell
Cell plate in
animal cell
Animal Mitosis -- Review
Interphase


Prophase


Metaphase


Anaphase


Telophase


Cytokinesis


Plant Mitosis -- Review
Interphase


Prophase


Metaphase


Anaphase


Telophase


Cytokinesis


Have the same number of
chromosomes as each other and
as the parent cell from which
they were formed
Identical to each other, but
smaller than parent cell
Must grow in size to become
mature cells (G
1
of Interphase)

32
33
Preceded by interphase which
includes chromosome replication
Two meiotic divisions --- Meiosis
I and Meiosis II
Called Reduction- division
Original cell is diploid (2n)
Four daughter cells produced that
are monoploid (1n)
34
Daughter cells contain half the
number of chromosomes as the
original cell
Produces gametes (eggs & sperm)
Occurs in the testes in males
(Spermatogenesis)
Occurs in the ovaries in females
(Oogenesis)

35
36
Start with 46 double stranded
chromosomes (2n)
After 1 division - 23 double
stranded chromosomes (n)
After 2nd division - 23 single
stranded chromosomes (n)
Occurs in our germ cells that
produce gametes
It is the fundamental basis of
sexual reproduction
Two haploid (1n) gametes are
brought together through
fertilization to form a diploid
(2n) zygote
37
Meiosis must reduce the chromosome number
by half
Fertilization then restores the 2n number

38
from mom from dad child
meiosis reduces
genetic content
too
much!
The right
number!
39
Homologs
separate
Sister
chromatids
separate
Diploid
Meiosis
I

Meiosis
II

Diploid
Haploid
40
1n =3
2n = 6
41
Nucleus
Spindle
fibers
Nuclear
envelope
Early
Prophase I
(Chromosome
number
doubled)
Late
Prophase
I
Metaphase
I
Anaphase
I
Telophase I
(diploid)
42
Early prophase
Homologs pair.
Crossing over
occurs.
Late prophase
Chromosomes condense.
Spindle forms.
Nuclear envelope
fragments.
43
Homologous chromosomes
(each with sister
chromatids)
Join to form a
TETRAD
Called Synapsis
Homologous
chromosomes in
a tetrad cross
over each other
Pieces of
chromosomes or
genes are
exchanged
Produces
Genetic
recombination in
the offspring
44
45
46
Crossing-over multiplies the already huge
number of different gamete types
produced by independent assortment
47
Homologous pairs
of chromosomes
align along the
equator of the
cell
48
Homologs separate and
move to opposite poles.

Sister chromatids remain
attached at their
centromeres.
49
Nuclear envelopes
reassemble.

Spindle disappears.

Cytokinesis divides cell
into two.
Only one homolog of each
chromosome is present in
the cell.
50
Meiosis II produces gametes with
one copy of each chromosome and
thus one copy of each gene.
Sister chromatids carry
identical genetic
information.
Gene X
51
Prophase
II
Metaphase
II
Anaphase
II
Telophase
II
4 Identical
haploid cells
52
Nuclear envelope
fragments.

Spindle forms.
53
Chromosomes align
along equator of cell.
54
Sister chromatids
separate and
move to opposite
poles.
Equator
Pole
55
Nuclear envelope
assembles.

Chromosomes
decondense.

Spindle disappears.

Cytokinesis divides
cell into two.
56
Gametes (egg & sperm)
form

Four haploid cells with
one copy of each
chromosome

One allele of each gene

Different combinations
of alleles for different
genes along the
chromosome
57
Oogenesis
or
Spermatogenesis
Occurs in the testes
Two divisions
produce 4
spermatids
Spermatids mature
into sperm
Men produce about
250,000,000 sperm
per day
58
59
Spermatid
60
Occurs in the ovaries
Two divisions produce 3 polar bodies
that die and 1 egg
Polar bodies die because of unequal
division of cytoplasm
Immature egg called oocyte
Starting at puberty, one oocyte
matures into an ovum (egg) every 28
days
61
62
63
Oogonium
(diploid)
Mitosis
Primary
oocyte
(diploid)
Meiosis I
Secondary
oocyte
(haploid)
Meiosis II
(if fertilization
occurs)
First polar body
may divide
(haploid)

Polar
bodies
die
Ovum (egg)
Second
polar body
(haploid)
a
A
X
X
a
X
A
X
a
X
a
X
Mature
egg
A
X
A
X
Should the gamete
with the chromosome
pair be fertilised
then the offspring
will not be normal.

In humans this often
occurs with the 21
st

pair producing a
child with Downs
Syndrome
G1/S
Monitors cell size and for DNA damage
G2/M
Replication complete, DNA damage?
M
Spindle fibers connected, etc.?
G0
Does body require more of my type of cell?
Cyclins and cyclin-dependent kinases (CDKs)
Cyclins synthesized and destroyed in a precise
pattern
A cyclin bind to a specific CDKs, activating it
Other proteins phosphorylated/activated
CDK4/cyclinD activate transcription factors for genes
such as DNA polymerase delta and DNA ligase
CDK1/cyclinB trigger events of early mitosis
(chromosome condensation, nuclear membrane
breakdown, etc.)
67
Parent Cell
Two
identical
daughter
cells
Tissues are not made up solely of
cells.
A substantial part of their volume is
extracellular space, which is largely
filled by an intricate network of
macromolecules constituting the
extracellular matrix.

This matrix is composed of a variety
of versatile proteins and
polysaccharides that are secreted
locally and assembled into an organized
meshwork in close association with the
surface of the cell that produced
them.
Extracellular Matrix
Extracellular matrix (ECM)
Secreted by animal cells, not plants
-surrounds animal cells
Composed of glycoproteins (or) proteoglycans
and fibrous proteins such as collagen and soluble
multiadhesive matrix proteins (e.g., fibronectin)
-may be connected to the cytoplasm via integrin
proteins present in the plasma membrane
Aids in support and recognition events
Extracellular matrix around muscle cells i.e.,
Basal lamina- is important in muscle cell function
and synapse formation


The extracellular matrix is composed of two
biochemically and morphologically separate
entities,

1. The basement membrane and

2. The interstitial connective tissue matrix

The Extracellular Matrix (ECM)

1. The Basement Membrane

Basement membranes are sheets of
extracellular matrix that separate epithelia
from mesenchyme. In adult tissues they
contain type IV collagen, noncollagenous
glycoproteins belonging to the family of
laminins, entactin and proteoglycans,
containing mostly heparan sulfate.

Basal lamina are synthesized by the cells that rest on it.

Four ubiquitous protein components are found in basal laminae

Type IV collagen, trimeric molecules with both rodlike and globular
domains that form a two-dimensional network

Laminins, a family of multiadhesive proteins that form a fibrous
two-dimensional network with type IV collagen and that also bind to
integrins

Entactin (also called nidogen), a rodlike molecule that cross-links
type IV collagen and laminin and helps incorporate other
components into the ECM

Perlecan, a large multidomain proteoglycan that binds to and
cross-links many ECM components and cell-surface molecules
The Basement Membrane- composition
Gels of polysaccharides and fibrous proteins
fill the interstitial space and act as a
compression buffer against the stress placed
on the ECM

This type of matrix contains interstitial
collagens of types I, III, V, VI, VII, XII
and others, as well as fibronectins and
proteoglycans, mostly of the chondroitin
sulfate and heparan sulfate types
2. The interstitial connective tissue matrix
Mechanical support
Scaffold (Temporary structure used to support )
Cohesion/Adhesion
Promotes epithelial formation
Embryonic development
Mechanism for Cellular Migration
Inflammation
Healing
Growth
Management of factors
Inflammation
Growth
Healing

COMPONENTS OF THE EXTRACELLULAR MATRIX

1. GLYCOSAMINOGLYCANS (GAGS) AND PROTEOGLYCANS
GAGS
Hyaluronan
Chondroitin sulfate, dermatan sulfate
Heparan sulfate, heparin
Keratan sulfate
PROTEOGLYCANS
Examples: Aggrecan, Decorin

2. STRUCTURAL PROTEINS
Collagen
Elastin

3. ADHESIVE PROTEINS
Fibronectin
Laminin

1. GLYCOSAMINOGLYCANS (GAGS) AND
PROTEOGLYCANS
COMPONENTS OF THE EXTRACELLULAR MATRIX
Glycosaminoglycans (mucopolysaccharides) are
linear polymers of repeating disaccharides.
The constituent monosaccharides tend to be
modified, with acidic groups, amino groups,
sulfated hydroxyl and amino groups, etc.
Glycosaminoglycans tend to be negatively charged,
because of the prevalence of acidic groups.

H
O
H
H
OH H
OH
COO

H
H
O
OH
H
H
NHCOCH
3
H
CH
2
OH
H
OO
D-glucuronate
O
1
2 3
4
5
6
1
2
3
4
5
6
N-acetyl-D-glucosamine
hyaluronate
Based on sugars groups, the type of linkage
between the sugars, and the number and
location of sulfate groups:
(1) hyaluronan
(2) chondroitin sulfate and dermatan sulfate
(3) heparan sulfate
(4) keratan sulfate
Hyaluronate (hyaluronan) is a glycosaminoglycan
with a repeating disaccharide consisting of 2 glucose
derivatives, glucuronate (glucuronic acid) & N-
acetyl-glucosamine.
The glycosidic linkages are b(13) & b(14).

H
O
H
H
OH H
OH
COO

H
H
O
OH
H
H
NHCOCH
3
H
CH
2
OH
H
OO
D-glucuronate
O
1
2 3
4
5
6
1
2
3
4
5
6
N-acetyl-D-glucosamine
hyaluronate
Heparan sulfate is initially synthesized on a
membrane-embedded core protein as a polymer of
alternating N-acetylglucosamine and
glucuronate residues.
Later, in segments of the polymer, glucuronate
residues may be converted to the sulfated sugar
iduronic acid, while N-acetylglucosamine residues
may be deacetylated and/or sulfated.

H
O
H
OSO
3

H
OH
H
COO

O
H
H
NHSO
3

H
OH
CH
2
OSO
3

H
H
H
O
O
heparin or heparan sulfate - examples of residues
iduronate-2-sulfate N-sulfo-glucosamine-6-sulfate
Proteoglycans are glycosaminoglycans that are
covalently linked to serine residues of specific
core proteins.
The glycosaminoglycan chain is synthesized by
sequential addition of sugar residues to the core
protein.
heparan sulfate
glycosaminoglycan

cytosol
core
protein
transmembrane
-helix
Proteoglycans are composed of GAGs
GAGs are composed of disaccharide units
Proteoglycan Aggregates
Huge Small Large
2. STRUCTURAL PROTEINS OF ECM

Collagen
Elastin
COMPONENTS OF THE EXTRACELLULAR MATRIX
Collagen : most abundant protein found in
the human body. About 1/3
rd
of the total
proteins.
Found abundantly in tendon, cartilage,
bone and skin
Functions:
cell migration
cell adhesion
molecular filtration
tissue repair
04/19/10
It has a triple-helix structure
containing three -polypeptide
chains arranged in right-handed
supercoil
Glycine, proline, hydroxyproline
1.5 nm diameter
At least 28 different collagens
found
The three -chains could be
same (collagen II) or different
(collagen I)
Collagen
molecule
Collagen Type

Tissue Distribution

Site of Synthesis

Main Function

Molecular
Organization

Fibril-Forming
Fibrillar









I


Skin, tendon,
Bone, fibrocartilage,
accounts for 90% of
body cartilage

Fibroblasts,
odontoblasts,
osteoblasts,
chondroblasts

Resistance to
tension

Fibril-forming
collagen

II

Hyaline cartilage,
intervertebral disk

Chondroblasts

Resistance to
pressure

Fibril-forming
collagen

III

Smooth muscle, blood
vessels, internal
organs, reticular
connective tissue

Smooth muscle cells,
reticular cells,
Schwann cells

Structural
maintenance in
expansible organs

Fibril-forming
collagen

V

Skin, tendon, bone,
fibrocartilage

Fibroblasts

Forms fibril with
type I

Fibril-forming
collagen

XI

Hyaline cartilage,
intervertebral disk

Chondroblasts

Forms fibril with
type II

Fibril-forming
collagen
Fibril-
Associated









IX

Hyaline cartilage

Chondroblasts

Fibril lateral
association

Fibril-associated
collagen

XII

Tendon, ligaments

Fibroblasts

Fibril lateral
association

Fibril-associated
collagen

Network-
Forming









IV

Basal laminae

Endothelial,
epithelial, muscle,and
Schwann cells

Sheetlike
network; Support
of delicate
structures,
filtration

Network-forming
collagen

VII

Beneath stratified
squamous



Anchoring Fibrils;
Binding cells to
subjacent
connective tissue

Anchoring collagen

Collagen Types
Elastin
Its relatively loose and unstructured polypeptide chains
are cross-linked covalently to generate a rubberlike
elastic meshwork that enables tissues such as
arteries and lungs to deform and stretch without
damage.
elastin
structure
Elastin
A fibrous protein
Important Youth Protein
Gives the skin its resiliency
Gives the skin the ability to
stretch and snap back into
shape
Elastin
Imparts
elasticity to
tissues
Super rubber
band
Highly cross-
linked
Major ECM of
arteries
Fibrillin covers
elastin fibers.
Fibrillin is
essential for
elasticity of
elastin
Fibronectin

Laminin
COMPONENTS OF THE EXTRACELLULAR MATRIX
Many different cell types synthesize
fibronectin, an abundant multiadhesive matrix
protein found in all vertebrates.

Fibronectins help attach cells to the
extracellular matrix by binding to other ECM
components, particularly fibrous collagens and
heparan sulfate proteoglycans, and to
cellsurface adhesion receptors such as
integrins.

Through their interactions with adhesion
receptors (e.g., integrin), fibronectins
influence the shape and movement of cells and
the organization of the cytoskeleton.
Fibronectin


Fibronectin
Fibronectins are dimers of two similar polypeptides linked at
their C-termini by two disulfide bonds
Arg-Gly-Asp (RGD) binds integrins: In Type III fibronectin
repeats

RGD
Laminin is one of the first extracellular matrix proteins synthesized
in a developing embryo, and early in development basal laminae
contain little or no type IV collagen and consist mainly of a laminin
network.

Laminin is a large (~850,000 daltons) flexible complex of three very
long polypeptide chains arranged in the shape of an asymmetric
cross and held together by disulfide bonds.

Like many other proteins in the extracellular matrix, it consists of a
number of functional domains: one binds to type IV collagen, one to
heparan sulfate, one to entactin, and two or more to laminin
receptor proteins on the surface of cells.

They also assist in cell adhesion. Laminins bind other ECM
components such as collagens, nidogens, and entactins.
Laminin
Laminin
Binds cells to the basal
lamina
Binding Domains for
Cells
PGs & GAGs
Collagen
Laminin, the principal multiadhesive matrix protein in
basal laminae, is a heterotrimeric, cross-shaped
protein with a total molecular weight of 820,000
Type IV Collagen in the Basal Lamina
Cell - extracellular matrix
e.g. during embyogenesis, matrix
molecules are involved in cell
migration and cell function

Cell - cell
e.g. lymphocytes interact with
antigen presenting cells

Cell - growth factor
Cell adhesion molecules (CAMs)
Cell adhesion molecules (CAMs) are cell
surface proteins involved in the interaction
of cell-cell or cell-extracellular matrix
.
CAMs take effect by the binding of receptor
and ligand.

Integrin family
Selectin family
Immunoglobulin (Ig) superfamily
Cadherin family
Mucin-like family
Other adhesion molecules
Cell-Cell Junction
Cell to cell
Gap junction
Tight junction
Anchoring junction
Desmosomes
Cell to matrix
Focal adhesions
Hemidesmosomes
Summary of Cell Junctions
Junctions
Tight Junctions
Adjacent cells are connected by impermeable junctions
called tight junctions.
Seal cells of an epithelial sheet to create a
permeability barrier. The tight junctions between
adjacent epithelial cells are usually located just below
the apical surface and help establish and maintain cell
polarity

These specialized regions of the plasma membrane form
a barrier that seals off body cavities such as the
intestine, the stomach lumen, the blood (e.g., the
bloodbrain barrier), and the bile duct in the liver.
Molecular Composition
Claudin: Transmembrane
Occludin: Transmembrane

Tight/Occluding Junctions
The two principal
integral-membrane
proteins found in tight
junctions are occludin
and claudin.
Tight junctions are composed of thin bands of
plasma membrane proteins that completely
encircle a polarized cell and are in contact
with similar thin bands on adjacent cells.

When thin sections of cells are viewed in an
electron microscope, the lateral surfaces of
adjacent cells appear to touch each other at
intervals and even to fuse in the zone just
below the apical surface
Tight Junctions
The tight junctions between the epithelial cells are thought to
block both kinds of diffusion.

First, they function as barriers to the diffusion of membrane
proteins between apical and basolateral domains of the plasma
membrane.

This undesirable diffusion of membrane constituents occurs if
tight junctions are disrupted, for example, by removing the
extracellular Ca2+ required for tight-junction integrity.

Second, they seal neighboring cells together so that water-
soluble molecules cannot leak between the cells: if a low-
molecular-weight tracer is added to one side of an epithelial cell
sheet, it will usually not pass beyond the tight junction
Functions of Tight Junctions
The role of tight junctions in
transcellular transport.
Transport proteins are confined to
different regions of the plasma
membrane in epithelial cells of the
small intestine. This segregation
permits a vectorial transfer of
nutrients across the epithelial sheet
from the gut lumen to the blood. In
the example shown, glucose is
actively transported into the cell by
Na
+
-driven glucose symports at the
apical surface, and it diffuses out of
the cell by facilitated diffusion
mediated by glucose carriers in the
basolateral membrane. Tight
junctions are thought to confine the
transport proteins to their
appropriate membrane domains by
acting as diffusion barriers within
the lipid bilayer of the plasma
membrane; these junctions also
block the backflow of glucose from
the basal side of the epithelium into
the gut lumen.
Tight junctions
Gap Junctions
A gap junction or nexus is a specialized
intercellular
connection between a multitude of animal cell-
types

Bridges the 2-4 nm gap between the neighbour
cells

It directly connects the cytoplasm of two cells,
which
allows various molecules and ions to pass freely
between cells

Gap junctions in the plasma membranes of
adjacent cells permit them to exchange small
molecules and to coordinate metabolic responses


The wall of the channel (transmembrane
proteins ) is composed by 6 connexins

Thus Hexagonal channel is formed i.e., connexon
(connexon from connexin)

The distribution of channels is tissue- or cell-specific
due to the difference of connexins

Accross channels substances are transmitted
(max MW. 1000) by a regulated mechanism
Gap junctions are constructed from
transmembrane proteins that form
structures called connexons.
Gap Junctions allow
cytoplasmic exchange
Connexons made up
of connexins

Thus connexons in the plasma membranes of
two cells in contact are aligned, they form a
continuous aqueous channel, which connects
the two cell interiors
Gap-junction channels do not remain continuously
open; instead, they flip
between open and closed states.
Allows for direct electrical communication between cells, although
different connexin subunits can impart different single channel
conductances

Allows for chemical communication between cells, through the
transmission of small second messengers, such as inositol triphosphate
(IP3) and calcium (Ca2+),although different connexin subunits can
impart different selectivity for particular small molecules.

Generally allows molecules smaller than 1,000 Daltons to pass
through, although different connexin subunits can impart different
pore sizes and different charge selectivity. Large biomolecules, for
example, nucleic acid and protein, are precluded from cytoplasmic
transfer between cells.

Ensures that molecules and current passing through the gap junction
do not leak into the intercellular space.

Properties of Gap junction
Anchoring
Junctions

Stabilize cells against mechanical stress

Mechanically attach cells and their cytoskeleton to
their neighbors or to the extracellular matrix

Desmosomes
A desmosome, also known as macula adherens
(Latin for adhering spot), is a cell structure
specialized for cell-to-cell adhesion

A type of junctional complex, they are localized
spot-like adhesions randomly arranged on the
lateral sides of plasma membranes.

Desmosomes help to resist shearing forces and
are found in simple and stratified squamous
epithelium. The intercellular space is very wide
(about 30 nm).

Desmosomes are also found in muscle tissue
where they bind muscles cells to one another.

Desmosomes
Desmosomes
Desmosomes are buttonlike points of intercellular
contact that rivet cells together

Inside the cell they serve as anchoring sites for
ropelike intermediate filaments, which form a
structural framework for the cytoplasmof great
tensile strength .

Thus, through desmosomes, the intermediate
filaments of adjacent cells are connected indirectly
to form a continuous network throughout the tissue.
Desmosomes: Cell-Cell Rivets
Hemidesmosomes
Half-Desmosomes

Hemidesmosomes similar in appearance to
desmosomes when visualized by electron
microscopy.
While desmosomes link two cells together,
hemidesmosomes attach one cell to the
extracellular matrix.

Rather than using cadherins,
hemidesmosomes use integrin cell adhesion
proteins.

Hemidesmosomes are asymmetrical and are
found in epithelial cells connecting the basal
face to other cells.
Hemidesmosomes
Half-Desmosomes

De: Desmosome
HD: Hemidesmosome
LD: Lamina Densa
Distribute forces on
an epithelium to the
basal lamina
Integrins mediate
basal lamina adhesion
Anchor proteins link
integrins to
intermediate
filaments via plectin
Difference between Desmosomes
and Hemidesmosomes