Cell Cycle and Mitosis

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LECTURE PRESENTATIONS

For CAMPBELL BIOLOGY, NINTH EDITION


Jane B. Reece, Lisa A. Urry, Michael L. Cain, Steven A. Wasserman, Peter V. Minorsky, Robert B. Jackson

The Cell Cycle

Lectures by
Erin Barley
Kathleen Fitzpatrick

© 2011 Pearson Education, Inc.


CELL CYCLE

• Actively dividing eukaryotic cells pass through


a series of stages.
• It is the complete series of events from one
cell division to the next.
• Consist of 2 phases.
Phases of the Cell Cycle
• The cell cycle consists of
– Mitotic (M) phase (mitosis and cytokinesis)
– Interphase (cell growth and copying of
chromosomes in preparation for cell division)

© 2011 Pearson Education, Inc.


• Interphase (about 90% of the cell cycle) can be
divided into subphases
– G1 phase (“first gap”)
– S phase (“synthesis”)
– G2 phase (“second gap”)
• The cell grows during all three phases, but
chromosomes are duplicated only during the S
phase

© 2011 Pearson Education, Inc.


Gap1 phase

• Metabolic changes prepare the cell for


division. At a certain point – the restriction
point – the cell is committed to division and
moves into the S phase.
• Excluding the chromosomes are duplicated.
• 10 hours duration
Insert drawing
Synthesis (S phase)

• DNA synthesis replicates the genetic


material. Each chromosomes now consist of
two sister chromatids.
• DNA replication and chromosomes
duplication occurs.
• 9 hours duration
Insert drawing
Gap2 phase

• Metabolic changes assemble the cytoplasmic


materials necessary for mitosis and
cytokinesis.
• Cell grows and prepares for mitosis.
• 4 hours duration
Insert drawing
Figure 12.6

INTERPHASE

G1 S
(DNA synthesis)

G2
G1 checkpoint

• The cell will be check if nutrients are


sufficient, grows factors are present, cell size
is adequate and DNA is not DAMAGED.
G2 phase

• Cell will be check if chromosomes replication


is complete and NO DNA DAMAGED AND
once that’s okay the cell will enter the M
phase.
• With the cell with 46 chromosomes and 92
chromatids will divide to produce two
daughter cells, two identical cells with 46
chromosomes and 46 chromatids.
• There are cells also that will go to cell cycle
arrest. These cells belongs to G0.
Cell
division
Overview: The Key Roles of Cell Division
• The ability of organisms to produce more of their
own kind best distinguishes living things from
nonliving matter
• The continuity of life is based on the reproduction
of cells, or cell division

© 2011 Pearson Education, Inc.


Mitosis

• The process by which duplicated


chromosomes are separated into two nuclei.
• 1 hour duration
• Mitosis with itself has a few phases within it. It
can be divided into 5 phases.
• Mitosis is conventionally divided into five phases
– Prophase
– Prometaphase
– Metaphase
– Anaphase
– Telophase
• Cytokinesis overlaps the latter stages of mitosis

© 2011 Pearson Education, Inc.


PROPHASE

• Chromosome materials condenses to form a compact mitotic


chromosome.
• The cytoskeleton disassembled and mitotic spindle is
assembled
• Nuclear envelop also dispersed.
Prometaphase

• Chromosomal microtubule attach to


kinetochore of chromosomes.
• Chromosomes are move to spindle equator
Metaphase

• Chromosomes are aligned along metaphase


plate, attached by chromosomal microtubules
to both tubules.
Anaphase

• Centromere split and chromatids separates


• Chromosomes move to opposite spindles
poles.
• Spindle poles move further apart.
Telophase

• Chromosomes are clustered at opposite


spindle poles.
• Chromosomes become disperse.
• Nuclear envelop will assembles
• Organelles will reforms.
CYTOKINESIS
Cytokinesis: A Closer Look
• In animal cells, cytokinesis occurs by a process
known as cleavage, forming a cleavage furrow
• In plant cells, a cell plate forms during cytokinesis

© 2011 Pearson Education, Inc.


Animation: Cytokinesis
Right-click slide / select ”Play”

© 2011 Pearson Education, Inc.


Figure 12.10c

Cleavage
furrow

100 m
Figure 12.UN01
P

G1 S
Cytokinesis
Mitosis G2

MITOTIC (M) PHASE

Prophase
Telophase and
Cytokinesis

Prometaphase
Anaphase
Metaphase
Meiosis I
Figure 12.1
• In unicellular organisms, division of one cell
reproduces the entire organism
• Multicellular organisms depend on cell division for
– Development from a fertilized cell
– Growth
– Repair
• Cell division is an integral part of the cell cycle,
the life of a cell from formation to its own division

© 2011 Pearson Education, Inc.


Figure 12.2
100 m (a) Reproduction

200 m
(b) Growth and
development

20 m
(c) Tissue renewal
Figure 12.2a

100 m (a) Reproduction


Figure 12.2b

200 m
(b) Growth and
development
Figure 12.2c

20 m
(c) Tissue renewal
Concept 12.1: Most cell division results in
genetically identical daughter cells
• Most cell division results in daughter cells with
identical genetic information, DNA
• The exception is meiosis, a special type of division
that can produce sperm and egg cells

© 2011 Pearson Education, Inc.


Cellular Organization of the Genetic
Material

• All the DNA in a cell constitutes the cell’s genome


• A genome can consist of a single DNA molecule
(common in prokaryotic cells) or a number of DNA
molecules (common in eukaryotic cells)
• DNA molecules in a cell are packaged into
chromosomes

© 2011 Pearson Education, Inc.


Figure 12.3

20 m
• Eukaryotic chromosomes consist of chromatin, a
complex of DNA and protein that condenses
during cell division
• Every eukaryotic species has a characteristic
number of chromosomes in each cell nucleus
• Somatic cells (nonreproductive cells) have two
sets of chromosomes
• Gametes (reproductive cells: sperm and eggs)
have half as many chromosomes as somatic cells

© 2011 Pearson Education, Inc.


Distribution of Chromosomes During
Eukaryotic Cell Division
• In preparation for cell division, DNA is replicated
and the chromosomes condense
• Each duplicated chromosome has two sister
chromatids (joined copies of the original
chromosome), which separate during cell division
• The centromere is the narrow “waist” of the
duplicated chromosome, where the two
chromatids are most closely attached

© 2011 Pearson Education, Inc.


Figure 12.4

Sister
chromatids

Centromere 0.5 m
• During cell division, the two sister chromatids of
each duplicated chromosome separate and move
into two nuclei
• Once separate, the chromatids are called
chromosomes

© 2011 Pearson Education, Inc.


Figure 12.5-1
Chromosomal
Chromosomes DNA molecules
1 Centromere

Chromosome
arm
Figure 12.5-2
Chromosomal
Chromosomes DNA molecules
1 Centromere

Chromosome
arm
Chromosome duplication
(including DNA replication)
and condensation
2

Sister
chromatids
Figure 12.5-3
Chromosomal
Chromosomes DNA molecules
1 Centromere

Chromosome
arm
Chromosome duplication
(including DNA replication)
and condensation
2

Sister
chromatids
Separation of sister
chromatids into
two chromosomes
3
• Eukaryotic cell division consists of
– Mitosis, the division of the genetic material in the
nucleus
– Cytokinesis, the division of the cytoplasm
• Gametes are produced by a variation of cell
division called meiosis
• Meiosis yields nonidentical daughter cells that
have only one set of chromosomes, half as many
as the parent cell

© 2011 Pearson Education, Inc.


Concept 12.2: The mitotic phase alternates
with interphase in the cell cycle
• In 1882, the German anatomist Walther Flemming
developed dyes to observe chromosomes during
mitosis and cytokinesis

© 2011 Pearson Education, Inc.


BioFlix: Mitosis
© 2011 Pearson Education, Inc.
Figure 12.7

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

Plasma
Nucleolus Nuclear membrane Chromosome, consisting Kinetochore Kinetochore Nuclear
envelope of two sister chromatids microtubule Spindle Centrosome at Daughter envelope
one spindle pole chromosomes forming
Figure 12.7a

G2 of Interphase Prophase 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
Figure 12.7b

Metaphase Anaphase Telophase and Cytokinesis

Metaphase Cleavage Nucleolus


plate furrow forming

Nuclear
Spindle Centrosome at Daughter envelope
one spindle pole chromosomes forming
Figure 12.7c

10 m
G2 of Interphase Prophase Prometaphase
Figure 12.7d

10 m
Metaphase Anaphase Telophase and Cytokinesis
Figure 12.7e
Figure 12.7f
Figure 12.7g
Figure 12.7h
Figure 12.7i
Figure 12.7j
The Mitotic Spindle: A Closer Look
• The mitotic spindle is a structure made of
microtubules that controls chromosome movement
during mitosis
• In animal cells, assembly of spindle microtubules
begins in the centrosome, the microtubule
organizing center
• The centrosome replicates during interphase,
forming two centrosomes that migrate to opposite
ends of the cell during prophase and
prometaphase

© 2011 Pearson Education, Inc.


• An aster (a radial array of short microtubules)
extends from each centrosome
• The spindle includes the centrosomes, the spindle
microtubules, and the asters

© 2011 Pearson Education, Inc.


• During prometaphase, some spindle microtubules
attach to the kinetochores of chromosomes and
begin to move the chromosomes
• Kinetochores are protein complexes associated
with centromeres
• At metaphase, the chromosomes are all lined up
at the metaphase plate, an imaginary structure at
the midway point between the spindle’s two poles

© 2011 Pearson Education, Inc.


Figure 12.8

Centrosome
Aster
Metaphase
Sister plate
chromatids (imaginary) Microtubules

Chromosomes
Kineto-
chores Centrosome
1 m

Overlapping
nonkinetochore
microtubules Kinetochore
microtubules

0.5 m
Figure 12.8a

Kinetochores

Kinetochore
microtubules

0.5 m
Figure 12.8b

Microtubules

Chromosomes

Centrosome

1 m
• In anaphase, sister chromatids separate and move
along the kinetochore microtubules toward
opposite ends of the cell
• The microtubules shorten by depolymerizing at
their kinetochore ends

© 2011 Pearson Education, Inc.


Figure 12.9
EXPERIMENT
Kinetochore

Spindle
pole

Mark

RESULTS

CONCLUSION
Chromosome
movement
Microtubule Kinetochore

Motor protein Tubulin


subunits
Chromosome
Figure 12.9a
EXPERIMENT
Kinetochore

Spindle
pole

Mark

RESULTS
Figure 12.9b

CONCLUSION
Chromosome
movement
Microtubule Kinetochore

Motor protein Tubulin


subunits
Chromosome
• Nonkinetochore microtubules from opposite poles
overlap and push against each other, elongating
the cell
• In telophase, genetically identical daughter nuclei
form at opposite ends of the cell
• Cytokinesis begins during anaphase or telophase
and the spindle eventually disassembles

© 2011 Pearson Education, Inc.


Animation: Animal Mitosis
Right-click slide / select ”Play”

© 2011 Pearson Education, Inc.


Animation: Sea Urchin (Time Lapse)
Right-click slide / select ”Play”

© 2011 Pearson Education, Inc.


Figure 12.10

(a) Cleavage of an animal cell (SEM) (b) Cell plate formation in a plant cell (TEM)

100 m
Cleavage furrow Vesicles Wall of parent cell
forming 1 m
cell plate Cell plate New cell wall

Contractile ring of Daughter cells


microfilaments
Daughter cells
Figure 12.10a
(a) Cleavage of an animal cell (SEM)

100 m
Cleavage furrow

Contractile ring of Daughter cells


microfilaments
Figure 12.10b
(b) Cell plate formation in a plant cell (TEM)

Vesicles Wall of parent cell


1 m
forming
cell plate Cell plate New cell wall

Daughter cells
Figure 12.10d

Vesicles Wall of parent cell 1 m


forming
cell plate
Figure 12.11

Chromatin
Nucleus condensing
10 m
Nucleolus Chromosomes Cell plate

1 Prophase 2 Prometaphase 3 Metaphase 4 Anaphase 5 Telophase


Figure 12.11a

Chromatin
Nucleus condensing
Nucleolus

10 m

1 Prophase
Figure 12.11b

Chromosomes

10 m

2 Prometaphase
Figure 12.11c

10 m

3 Metaphase
Figure 12.11d

10 m

4 Anaphase
Figure 12.11e

10 m
Cell plate

5 Telophase
Binary Fission in Bacteria
• Prokaryotes (bacteria and archaea) reproduce by
a type of cell division called binary fission
• In binary fission, the chromosome replicates
(beginning at the origin of replication), and the
two daughter chromosomes actively move apart
• The plasma membrane pinches inward, dividing
the cell into two

© 2011 Pearson Education, Inc.


Figure 12.12-1
Origin of Cell wall
replication Plasma membrane
E. coli cell
Bacterial chromosome
1 Chromosome Two copies
replication of origin
begins.
Figure 12.12-2
Origin of Cell wall
replication Plasma membrane
E. coli cell
Bacterial chromosome
1 Chromosome Two copies
replication of origin
begins.

2 Replication Origin Origin


continues.
Figure 12.12-3
Origin of Cell wall
replication Plasma membrane
E. coli cell
Bacterial chromosome
1 Chromosome Two copies
replication of origin
begins.

2 Replication Origin Origin


continues.

3 Replication
finishes.
Figure 12.12-4
Origin of Cell wall
replication Plasma membrane
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.
The Evolution of Mitosis
• Since prokaryotes evolved before eukaryotes,
mitosis probably evolved from binary fission
• Certain protists exhibit types of cell division that
seem intermediate between binary fission and
mitosis

© 2011 Pearson Education, Inc.


Figure 12.13
Bacterial
(a) Bacteria
chromosome

Chromosomes

Microtubules
(b) Dinoflagellates

Intact nuclear
envelope

Kinetochore
microtubule
(c) Diatoms and
some yeasts Intact nuclear
envelope

Kinetochore
microtubule
(d) Most eukaryotes
Fragments of
nuclear envelope
Figure 12.13a

Bacterial
chromosome

(a) Bacteria

Chromosomes

Microtubules

Intact nuclear
envelope
(b) Dinoflagellates
Figure 12.13b

Kinetochore
microtubule

Intact nuclear
envelope

(c) Diatoms and some yeasts

Kinetochore
microtubule

Fragments of
nuclear envelope
(d) Most eukaryotes
Concept 12.3: The eukaryotic cell cycle is
regulated by a molecular control system
• The frequency of cell division varies with the type
of cell
• These differences result from regulation at the
molecular level
• Cancer cells manage to escape the usual controls
on the cell cycle

© 2011 Pearson Education, Inc.


Evidence for Cytoplasmic Signals
• The cell cycle appears to be driven by specific
chemical signals present in the cytoplasm
• Some evidence for this hypothesis comes from
experiments in which cultured mammalian cells at
different phases of the cell cycle were fused to
form a single cell with two nuclei

© 2011 Pearson Education, Inc.


Figure 12.14
EXPERIMENT
Experiment 1 Experiment 2

S G1 M G1

RESULTS

S S M M
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 nucleus immediately
immediately entered began mitosis—a spindle
the S phase—DNA formed and chromatin
was synthesized. condensed, even though
the chromosome had not
been duplicated.
The Cell Cycle Control System
• The sequential events of the cell cycle are directed
by a distinct cell cycle control system, which is
similar to a clock
• The cell cycle control system is regulated by both
internal and external controls
• The clock has specific checkpoints where the cell
cycle stops until a go-ahead signal is received

© 2011 Pearson Education, Inc.


Figure 12.15
G1 checkpoint

Control
system S
G1

M G2

M checkpoint
G2 checkpoint
• For many cells, the G1 checkpoint seems to be the
most important
• If a cell receives a go-ahead signal at the G1
checkpoint, it will usually complete the S, G2, and
M phases and divide
• If the cell does not receive the go-ahead signal, it
will exit the cycle, switching into a nondividing
state called the G0 phase

© 2011 Pearson Education, Inc.


Figure 12.16

G0
G1 checkpoint

G1 G1

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


signal. go-ahead signal.
The Cell Cycle Clock: Cyclins and Cyclin-
Dependent Kinases
• Two types of regulatory proteins are involved in
cell cycle control: cyclins and cyclin-dependent
kinases (Cdks)
• Cdks activity fluctuates during the cell cycle
because it is controled by cyclins, so named
because their concentrations vary with the cell
cycle
• MPF (maturation-promoting factor) is a cyclin-Cdk
complex that triggers a cell’s passage past the G2
checkpoint into the M phase
© 2011 Pearson Education, Inc.
Figure 12.17
M G1 S G2 M G1 S G2 M G1
MPF activity
Cyclin
concentration

Time
(a) Fluctuation of MPF activity and cyclin concentration
during the cell cycle

Cdk

Degraded
cyclin G2 Cdk
checkpoint
Cyclin is
degraded
Cyclin
MPF

(b) Molecular mechanisms that help regulate the cell cycle


Figure 12.17a

M G 1 S G2 M G1 S G2 M G1
MPF activity
Cyclin
concentration

Time
(a) Fluctuation of MPF activity and cyclin concentration
during the cell cycle
Figure 12.17b

Cdk

Degraded
cyclin G2 Cdk
checkpoint
Cyclin is
degraded
MPF Cyclin

(b) Molecular mechanisms that help regulate the cell cycle


Stop and Go Signs: Internal and External
Signals at the Checkpoints
• An example of an internal signal is that
kinetochores not attached to spindle microtubules
send a molecular signal that delays anaphase
• Some external signals are growth factors,
proteins released by certain cells that stimulate
other cells to divide
• For example, platelet-derived growth factor
(PDGF) stimulates the division of human fibroblast
cells in culture

© 2011 Pearson Education, Inc.


Figure 12.18

1 A sample of human Scalpels


connective tissue is
cut up into small
pieces.
Petri
dish
2 Enzymes digest
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


Figure 12.18a

10 m
• A clear example of external signals is density-
dependent inhibition, in which crowded cells
stop dividing
• Most animal cells also exhibit anchorage
dependence, in which they must be attached to a
substratum in order to divide
• Cancer cells exhibit neither density-dependent
inhibition nor anchorage dependence

© 2011 Pearson Education, Inc.


Figure 12.19

Anchorage dependence

Density-dependent inhibition

Density-dependent inhibition

20 m 20 m
(a) Normal mammalian cells (b) Cancer cells
Figure 12.19a

20 m
Figure 12.19b

20 m
Loss of Cell Cycle Controls in Cancer Cells
• Cancer cells do not respond normally to the body’s
control mechanisms
• Cancer cells may not need growth factors to grow
and divide
– They may make their own growth factor
– They may convey a growth factor’s signal without
the presence of the growth factor
– They may have an abnormal cell cycle control
system

© 2011 Pearson Education, Inc.


• A normal cell is converted to a cancerous cell by a
process called transformation
• Cancer cells that are not eliminated by the
immune system form tumors, masses of abnormal
cells within otherwise normal tissue
• If abnormal cells remain only at the original site,
the lump is called a benign tumor
• Malignant tumors invade surrounding tissues and
can metastasize, exporting cancer cells to other
parts of the body, where they may form additional
tumors
© 2011 Pearson Education, Inc.
Figure 12.20

Lymph
vessel
Tumor
Blood
vessel

Glandular Cancer
tissue cell
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.
• Recent advances in understanding the cell
cycle and cell cycle signaling have led to
advances in cancer treatment

© 2011 Pearson Education, Inc.


Figure 12.21
Figure 12.UN02
Figure 12.UN03
Figure 12.UN04
Figure 12.UN05
Figure 12.UN06

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