Chapter 12:

The Cell Cycle

1. Overview of Cell Division

2. Mitosis & Cytokinesis

3. Cell Cycle Regulation

Roles of Cell Division
100 m (a) Reproduction

200 m
(b) Growth and
development

20 m
(c) Tissue renewal
 Bacterial Cell Division
Origin of Cell wall
Binary replication Plasma membrane

Fission E. coli cell

Bacterial chromosome
1 Chromosome Two copies
replication of origin
begins.

2 Replication Origin Origin

continues.

3 Replication
finishes.

4 Two daughter
cells result.
 Eukaryotic Cell Division
Haploid gametes (n = 23) Meiosis
• occurs in gamete
production
n
Egg cell (sperm & egg)
n
Sperm cell • ½ the normal
Meiosis fertilization chromosome #
(haploid or “1n”)
Diploid • generates cells that are
zygote genetically unique
(2n = 46) 2n
Multicellular Mitosis
diploid adults
(2n = 46) • occurs in somatic
cells (all cells
except gametes)
Mitosis and • generates cells
development genetically identical
to original cell
 Chromosomes
CHROMOSOME:
a distinct piece of DNA
in a cell

CHROMATIN:
DNA complexed with
histone proteins
20 m

Sister
Chromatin
chromatids can be in a
condensed or
uncondensed
state.
Centromere 0.5 m
 Chromosome
Content
• somatic cells
are diploid (2n)
• 2 of each
chromosome
• i.e., 1 from each
parent

• gametes are
haploid (1n)
• 1 of each
chromosome
karyotype of human male
 Chromosome Duplication
Chromosomal
Chromosomes DNA molecules
• before cell division,
1 Centromere
chromosomes are
copied by the process
of DNA replication Chromosome
arm

Chromosome duplication
• the identical copies (including DNA replication)
and condensation
(sister chromatids)
2
are connected via
cohesin proteins at
the region of the Sister
chromatids
chromosome called
Separation of sister
the centromere chromatids into
two chromosomes
3
Still considered a single
chromosome until sister
chromatids separate.
The Cell Cycle
INTERPHASE

G1 S
(DNA synthesis)

G2
 Stages of the Cell Cycle
G1:
• preparation for DNA replication
• non-dividing cells are arrested at this stage of
the cell cycle (referred to as G0)
S phase:
• replication of genetic material (DNA Synthesis)
G2:
• preparation for cell division
M phase:
• cell division (Mitosis or Meiosis)
***G1, S & G2 collectively make up “Interphase”***
 Stages of Mitosis

10 m
G2 of Interphase Prophase Prometaphase Metaphase Anaphase Telophase & Cytokinesis
Centrosomes Chromatin Early Fragments Nonkinetochore
(with centriole (duplicated) mitotic Aster of nuclear microtubules Metaphase Cleavage Nucleolus
pairs) spindle envelope plate furrow forming
Centromere

Plasma
membrane
Nucleolus Nuclear Chromosome, Kinetochore Kinetochore Nuclear
envelope Consisting of two microtubule Spindle Centrosome at Daughter envelope
sister chromatids one spindle pole chromosomes forming

Prophase > Prometaphase > Metaphase >

Anaphase > Telophase
• results in the division of the cell nucleus
• the cell may or may not undergo cytokinesis
 G2 of G 2 of Interphase
Interphase Prophase
Prophase Prometaphase
Prometaphase
Centrosomes Fragments
(with centriole Chromatin Early mitotic Aster of nuclear Nonkinetochore
pairs) (duplicated) spindle envelope microtubules
Centromere

Plasma
Nucleolus membrane Kinetochore Kinetochore
Chromosome, consisting
Nuclear of two sister chromatids microtubule
envelope
Interphase
• G1, S phase & G2 (all events in preparation for cell division)

Prophase
• duplicated chromosomes begin to condense
• mitotic spindle begins to form
• nucleoli disappear
• centrosomes move toward opposite poles

Prometaphase
• nuclear envelope breaks down
• microtubules penetrate nuclear region, begin to
attach to kinetochores of chromosomes
• other microtubules interact from opposite poles
 Metaphase
Metaphase Anaphase
Anaphase Telophase
Telophase and Cytokinesis
and Cytokinesis

Metaphase Cleavage Nucleolus

plate furrow forming

Nuclear
Spindle Centrosome at Daughter envelope
one spindle pole chromosomes forming
Metaphase
• alignment of duplicated chromosomes along
the metaphase plate of the cell
• centrosomes now at opposite poles

Anaphase
• cohesins connecting sister chromatids cleaved
• microtubules mediate separation of sister
chromatids and elongation of the cell

Telophase
• opposite of prophase
• chromosomes decondense, nuclear envelope reforms
spindle fibers disassemble, nucleoli reappear
 The Mitotic Spindle
Centrosome
Aster
Metaphase
Sister plate
chromatids (imaginary) Microtubules

Chromosomes
Kineto-
chores Centrosome
1 m

Overlapping
nonkinetochore
Kinetochore microtubules
microtubules
Kinetochore shorten while non-kinetochore
microtubules microtubules “push” against
each other to extend the cell.

0.5 m
EXPERIMENT
Kinetochore
Shortening of
Spindle
pole
Microtubules
Mark • microtubules are
labeled with a
fluorescent dye
RESULTS
• “bleach” region of
microtubules (via laser)
to mark them
• observe shortening of
CONCLUSION microtubules relative
Chromosome
movement
to mark
Microtubule Kinetochore
Revealed that kinetochore
Motor protein Tubulin
subunits microtubules shorten at the
Chromosome kinetochore end.
 (a) Cleavage of an animal cell (SEM)
Cytokinesis in
Animal Cells
• actin microfilaments
form a contractile
ring at the center of
the cell inside the
plasma membrane
100 m
• motor proteins drive Cleavage furrow

the contraction of the

ring, forming a
cleavage furrow
which eventually
fuses resulting in
2 separate cells! Contractile ring of Daughter cells
microfilaments
 Mitosis in Plant Cells
Chromatin
Nucleus condensing
10 m
Nucleolus Chromosomes Cell plate

1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase

The stages of mitosis in plants are

essentially the same as in animal cells.
(b) Cell plate formation in a plant cell (TEM)
Cytokinesis in
Plant Cells

• vesicles transport
new cell wall material
to the middle of cell
Vesicles Wall of parent cell 1 m
forming
cell plate Cell plate New cell wall • cell plate begins to
form, eventually
becoming a complete
cell wall separating
the 2 daughter cells

Daughter cells
 General Cell Cycle Features
Proceeds in only 1 direction:
G1 > S > G2 > M > G1 > S > G2 > M > …

Controlled (internally) by Cyclins & Cyclin

Dependent Kinases (CDK’s)
• extracellular signals influence cyclin & CDK
activity (i.e., cell division)

Each phase of the cell cycle has characteristic

“check points”
• ensures cell cycle progression only when
appropriate
Checkpoints in the Cell Cycle
G1 checkpoint

Control
system S
G1

M G2

M checkpoint
G2 checkpoint
 The G1 Checkpoint
This is the key checkpoint determining if the cell will
remain in G0 or commit to dividing by entering G1.

G0
G1 checkpoint

G1 G1

(a) Cell receives a go-ahead (b) Cell does not receive a

signal. go-ahead signal.
 Cytoplasmic Factors Control Cell Cycle
EXPERIMENT
Experiment 1 Experiment 2
Experiment 1
S phase cytoplasm
causes G1 cell to
S G1 M G1 enter S phase
RESULTS
Experiment 2
M phase cytoplasm
causes G1 cell to
S S M M
enter M phase
When a cell in the S When a cell in the
phase was fused M phase was fused with
with a cell in G1, a cell in G1, the G1
the G1 nucleus
immediately entered
nucleus immediately
began mitosis—a spindle
These “cytoplasmic
the S phase—DNA formed and chromatin factors” move the cell
was synthesized. condensed, even though
the chromosome had not forward, not backward,
been duplicated. in the cell cycle.
 G2 G2
M G1 S
MPF activity
M G1 S M G1
Cyclins, CDKs
Cyclin
concentration & Cell Cycle
Progression
Time
(a) Fluctuation of MPF activity and cyclin concentration
during the cell cycle Maturation Promoting
Factor (MPF) = complex
of cyclin protein & CDK

• this particular cyclin-CDK

complex mediates
Cdk passage from G2 into
M phase
Degraded
cyclin G2 Cdk
Cyclin is
checkpoint • other cyclin-CDK
degraded complexes mediate
Cyclin
MPF passage to other stages
of the cell cycle
(b) Molecular mechanisms that help regulate the cell cycle
 Cyclins & CDK Activity
Cyclins control CDK activity:
• CDK’s are only active when complexed with a
cyclin
• able to phosphorylate appropriate substrates

• cyclin levels fluctuate in a regular pattern

throughout the cell cycle
• CDK levels are constant

• cyclins also determine CDK substrates

 The Amount of
Cyclin Oscillates
during cell cycle

• add labeled amino acid

to synchronous cells
• remove regular samples

• run on a gel

• cyclins seen to oscillate

• undergo periodic
degradation
 Growth Factors
Most cells require “growth factors” to re-enter the cell cycle.
1 A sample of human Scalpels
connective tissue is
cut up into small Growth factors
pieces. are soluble
signaling
Petri molecules that
dish
result in cells
2 Enzymes digest
entering G1.
the extracellular
matrix, resulting in
a suspension of
free fibroblasts.
4 PDGF is added 10 m
3 Cells are transferred to to half the
culture vessels. vessels.

Without PDGF With PDGF

 Contact Inhibition
Anchorage dependence Normal cells exit
the Cell Cycle
when in contact
with neighboring
Density-dependent inhibition cells, cancer cells
do not.

Density-dependent inhibition

20 m 20 m
(a) Normal mammalian cells (b) Cancer cells
 What is Cancer?
It is a deadly disease due to the loss of
cell cycle regulation caused largely by
somatic mutations in key genes.
• individuals do not inherit cancer although
they may inherit varying degrees of
predisposition to cancer

• can be manifested in many different ways

• exhibits varying degrees of virulence

depending on factors such as metastasis
and vascularization of the cancer tissue
 Cancer requires “Multiple Hits”
Prevailing evidence indicates that “one
mutant gene does not a cancer make…”
• mutations in multiple genes are typically
necessary for a cancer cell to survive and
proliferate

• individuals may inherit some of these mutant

genes, but more must be “hit” for a cell to
become cancerous

• this is an extremely rare event, but all it takes is

1 cell to produce a cancer
Stages in Cancer Development

1b

4 3 The sequential
acquisition
of these
characteristics
is typical of
many cancers:
5 2

1a
 Metastasis
Metastasis: spread of cancer cells from the original
tumor to other locations in the body.

Lymph
vessel
Tumor
Blood
vessel

Cancer
Glandular cell
tissue
Metastatic
tumor
1 A tumor grows 2 Cancer 3 Cancer cells spread 4 Cancer cells
from a single cells invade through lymph and may survive
cancer cell. neighboring blood vessels to and establish
tissue. other parts of the a new tumor
body. in another part
of the body.
Cancers Increase Dramatically with Age

consistent
with
“multi-hit”
hypothesis
 Key Terms for Chapter 12
• cell cycle, mitosis, meiosis, binary fission
• haploid, diploid, somatic cell, gamete
• interphase, prophase, metaphase, prometaphase,
anaphase, telophase, cytokinesis

• centromere, centrosome, kinetochore, cohesin

• chromosome, chromatin, chromatid, sister chromatid

• spindle, aster, cytokinesis

• cleavage furrow, contractile ring, cell plate Relevant

• checkpoint, cyclin, CDK, metastasis,
Chapter
angiogenesis Questions
• contact inhibition, growth factor 1-11