1. The Cell Cycle
Dr. Jorge Rodríguez

2. 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
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3. Cell division plays several important roles
in life
• In unicellular organisms (proka- or eukaryotes),
division of one cell reproduces the entire
organism
• Multicellular organisms depend on cell division
for
– Reproduction - Development from a fertilized
cell
– Growth and development
– Repair of tissues
• Cell division is an integral part of the cell cycle,
© 2011 Pearson Education, Inc.

4. Figure 12.2
100 µm
(a) Reproduction
Amoeba, dividing into two cells
200 µm
(b) Growth and
development
Sand dollar, embryo shortly
after fertilized egg divided
20 µm
Dividing bone marrow cells
(c) Tissue renewal

5. 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.

6. 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)
• Before the cell can divide this DNA must be copied
or replicated and separated to two daughter cells
© 2011 Pearson Education, Inc.

7. Figure 12.3
20 µm
DNA molecules in a cell are packaged into chromosomes

8. Figure 6.9a
Nucleus
Nucleolus
Chromatin
Nuclear envelope:
Inner membrane
Outer membrane
Nuclear pore
Rough ER
Pore
complex
Ribosome
Close-up
of nuclear
envelope
Chromatin
Eukaryotic chromosome consists of one very long, DNA molecule
associated with proteins.

9. DNA molecule carries several hundreds to a few
thousand genes

10. The associated proteins mantain the structure of the
chromosome and help control the activities of the genes
Eukaryotic chromosomes consist of chromatin, a
complex of DNA and protein that condenses during cell
division

11. • Every eukaryotic species has
a characteristic number of
chromosomes in each cell
nucleus
• Somatic cells (body 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.

12. 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
– Attached along their lenghts by protein complex called
cohesins (cohesinas)
One sister
chromatid
Sister
chromatids
Centromere
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0.5 µm

13. • The centromere is the narrow “waist” of the duplicated
chromosome, where the two chromatids are most closely
attached
• The part of a chromatid on either side of the centromere is
referred to as arm of the chromatid
Sister
chromatids
Centromere
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0.5 µm

14. • 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.

15. Figure 12.5-3
Chromosomes
1
Chromosomal
DNA molecules
Centromere
Chromosome
arm
Chromosome duplication
(including DNA replication)
and condensation. Two sister
chromatids are formed
2
Sister
chromatids
Separation of sister
chromatids into
two chromosomes
3

16. • 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
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17. 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
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18. 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)
– Mitosis is the shortest and interphase is the
longer stage of the cell cycle
© 2011 Pearson Education, Inc.

19. • 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 producing
organelles, but chromosomes are duplicated only
during the S phase
© 2011 Pearson Education, Inc.

20. Figure 12.6
The cell cycle
INTERPHASE
S
G1, first part of interphase,
followed by S
(M)
P
sis
i
Mi
to
k
to
Cy
MIT
O
sis
ne
(DNA synthesis and
chromosome duplication)
G2
T
HAS IC
E
MITOTIC (M) PHASE, alternate
with interphase
• M phase, daughter cromosomes in daugther
nuclei.
• Cytokinesis, divide the cytoplasm into 2
daugther cells.
• Relative duration of the phases may vary.

21. • Mitosis is conventionally divided into five phases
–
–
–
–
–
Prophase
Prometaphase
Metaphase
Anaphase
Telophase
• Cytokinesis overlaps the latter stages of mitosis
completing the mitotic stages
© 2011 Pearson Education, Inc.

22. Figure 12.7a
G2 of Interphase
Centrosomes
(with centriole
pairs)
Prometaphase
Prophase
Fragments
Chromatin Early mitotic Aster
of nuclear
(duplicated) spindle
Centromere envelope
Plasma
membrane
Nucleolus
Nuclear
envelope
• Sobre nuclear rodea el núcleo.
• Nucleoli (s) present.
• 2 centrosomas formados por
duplicación de cada cromosoma.
• Chromosomes not condensed.
Chromosome, consisting
of two sister chromatids
Nonkinetochore
microtubules
Kinetochore
Kinetochore
microtubule
• Chromatin become condensed.
• Envelope fragments.
• Nucleoli dissapear.
• Microtubules invade
nuclear area.
• Each chromosome appears as two
sister chromatids.
• Mitotic spindle begins to form.
Composed by centrosomes and
microtubules.
• Kinetochore appears at
centromeres.
• Kinetochore microtubules
forming.
• Asters, radial arrays of microtubules. • Nonkinetochore
microtubules forms the
• Centrosomes move away.
opposite pole of the

23. Figure 12.7b
Metaphase
Anaphase
Metaphase
plate
Spindle
Telophase and Cytokinesis
Cleavage
furrow
Centrosome at
one spindle pole
Daughter
chromosomes
Nucleolus
forming
Nuclear
envelope
forming
• Two nuclei forms in the cell.
• Centrosomes at opposite poles
of the cell.
• Chromosomes at metaphase
plate.
• Shortest phase.
• Nuclear envelopes arises.
• Cohesins are cleaved.
• Nucleoli reappear.
• Sister chromatids separates. • Chromosomes less condensed.
• Daugther chromosomes
moves towards opposite
poles.
• Depolymerization of microtubules.
• Cell elongates.
• Cytokinesis under way by late
telophase. Formation of cleavage
furrow.
• Mitosis is completed.

24. Figure 12.UN01
INTERPHASE
G1
S
Cytokinesis
G2
Mitosis
MITOTIC (M) PHASE
Prophase
Telophase and
Cytokinesis
Prometaphase
Anaphase
Metaphase

25. Figure 12.7a
The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)
Chromatin
(duplicated)
Plasma
membrane
Nucleolus
Nuclear
envelope
•
•
•
•
•
Prometaphase
Prophase
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
Many events of mitosis depend on the mitotic spindle
Begins to form in the cytoplasm during prophase
The mitotic spindle is a structure made of fibers and associated proteins
The spindle polymerize by incorporating subunits of tubulin
Controls chromosome movement during mitosis

27. Figure 12.7a
The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)
Chromatin
(duplicated)
Plasma
membrane
Nucleolus
Nuclear
envelope
•
•
•
Prometaphase
Prophase
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
In animal cells, assembly of spindle microtubules begins in the centrosome, a
subcellular region the microtubule organizing center
– A pair of centrioles is located at the center of the centrosomes, not
essential for cell division
The centrosome replicates during interphase, forming two centrosomes
As spindle microtubules grows, centrosomes migrate to opposite ends of the
cell during prophase and prometaphase

28. Figure 12.7a
The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)
Chromatin
(duplicated)
Plasma
membrane
Nucleolus
Nuclear
envelope
•
•
Prometaphase
Prophase
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
An aster (a radial array of short microtubules) extends from each
centrosome
The spindle includes the centrosomes, the spindle microtubules, and
the asters

29. Figure 12.7a
The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)
Chromatin
(duplicated)
Plasma
membrane
Nucleolus
Nuclear
envelope
Prometaphase
Prophase
Early mitotic
spindle
Aster
Centromere
Chromosome, consisting
of two sister chromatids
Fragments
of nuclear
envelope
Kinetochore
Nonkinetochore
microtubules
Kinetochore
microtubule
• During prometaphase, some spindle microtubules attach
to the kinetochores of chromosomes and begin to move the
chromosomes
 Kinetochores microtubules
• Kinetochores are protein complexes (2) associated with
centromeres in each sister chromatids

30. Figure 12.7b
Metaphase
Anaphase
Metaphase
plate
Spindle
Centrosome at
one spindle pole
Telophase and Cytokinesis
Cleavage
furrow
Daughter
chromosomes
Nucleolus
forming
Nuclear
envelope
forming
• 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
• The spindle is completed when microtubules of the asters
attach to the plasma membrane

31. Figure 12.8
Aster
Centrosome
Sister
chromatids
Metaphase
plate
(imaginary)
Microtubules
Chromosomes
Kinetochores
Centrosome
1 µm
Overlapping
nonkinetochore
microtubules
Kinetochore
microtubules
•
0.5 µm
•
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
The spindle is completed when
microtubules of the asters attach to the
plasma membrane

32. Figure 12.UN04

33. Figure 12.7b
Metaphase
Anaphase
Metaphase
plate
Spindle
•
•
•
Centrosome at
one spindle pole
Telophase and Cytokinesis
Cleavage
furrow
Daughter
chromosomes
Nucleolus
forming
Nuclear
envelope
forming
In anaphase, cohesins are cleaved by separases
Sister chromatids separate and move along the kinetochore
microtubules toward opposite ends of the cell
The microtubules shorten by depolymerizing at their kinetochore ends

34. Figure 12.7b
Metaphase
Anaphase
Metaphase
plate
Spindle
•
•
•
•
Centrosome at
one spindle pole
Telophase and Cytokinesis
Cleavage
furrow
Daughter
chromosomes
Nucleolus
forming
Nuclear
envelope
forming
In anaphase, nonkinetochore microtubules from opposite poles overlap and
push against each other, elongating the cell
At the end of anaphase, duplicate chromosomes have arrived at opposite ends
of elongated parent 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 by depolymerization

35. Cytokinesis: A Closer Look
• In animal cells, cytokinesis occurs by a process
known as cleavage, forming a cleavage furrow
(surco o hendedura)
• In plant cells, a cell plate forms during cytokinesis
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36. Figure 12.10a
(a) Cleavage of an animal cell (SEM)
Cleavage furrow
(old metaphase plate)
100 µm
Contractile ring of microfilaments Daughter cells (cytosol, nucleus, organelles,
(actin and myosin)
subcellular structures)

37. (b) Cell plate formation in a plant cell (TEM)
• No cleavage furrow formed.
• Telophase, vesicles from
Golgi move to the middle of the
cell, coalesce and produce a
cell plate.
Vesicles
forming
cell plate
Wall of parent cell
Cell plate
1 µm
New cell wall
Daughter cells
• Vesicles contains cell wall
material and fuses with the
plasma membrane.
• Two daugther cells result.
Figure 12.10b

38. Binary Fission in Bacteria
• Prokaryotes (bacteria and archaea) reproduce by
a type of cell division called binary fission
• In binary fission, bacteria grows and 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
• Binary fission in single-celled eukaryotes such as amoeba
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39. Figure 12.12-1
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
Cell wall
Plasma membrane
Bacterial chromosome
Two copies
of origin
 Chromosome replicates (beginning at the origin
of replication), and the two daughter chromosomes
actively move apart (not understood).

40. Figure 12.12-2
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
2 Replication
continues.
Cell wall
Plasma membrane
Bacterial chromosome
Two copies
of origin
Origin
Origin
• One copy of each origin at each end of the cell.
• Cell elongates.

41. Figure 12.12-3
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
2 Replication
continues.
Cell wall
Plasma membrane
Bacterial chromosome
Two copies
of origin
Origin
Origin
3 Replication
finishes.
Plasma membrane grows inward, a new cell wall is
formed.

42. Figure 12.12-4
Origin of
replication
E. coli cell
1 Chromosome
replication
begins.
2 Replication
continues.
3 Replication
finishes.
4 Two daughter
cells result.
Cell wall
Plasma membrane
Bacterial chromosome
Two copies
of origin
Origin
Origin

44. The eukaryotic cell cycle is regulated by a
molecular control system
• The frequency of cell division varies with the type
of cell
– Timing and rate of cell division are crucial to
growth, development and maintenance in different
parts of the cell
• These cell cycle differences result from regulation
at the molecular level
• Cancer cells manage to escape the usual controls
on the cell cycle
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45. 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
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46. Figure 12.14
EXPERIMENT
Experiment 1
S
G1
S
S
Experiment 2
M
G1
RESULTS
When a cell in the S
phase was fused
with a cell in G1,
the G1 nucleus
immediately entered
the S phase—DNA
was synthesized.
M
M
When a cell in the
M phase was fused with
a cell in G1, the G1
nucleus immediately
began mitosis—a spindle
formed and chromatin
condensed, even though
the chromosome had not
been duplicated.
Conclusion: The results of fusing a G1 with a S or M cell cycle
suggest that molecules present in the cytoplasm during S or
M phase control the progression to those phases.

47. 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
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48. Figure 12.15
G1 checkpoint
Control
system
G1
M
M checkpoint
S
G2
G2 checkpoint
Three major checkpoints:
G1, G2, M phases

49. Figure 12.16
G0
G1 checkpoint
G1
(a) Cell receives a go-ahead
signal.
G1
(b) Cell does not receive a
go-ahead signal.
•
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

50. The Cell Cycle Clock: Cyclins and CyclinDependent 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
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51. Figure 12.17a
MPF (maturation-promoting factor) is a cyclin-Cdk
complex that triggers a cell’s passage past the G2
checkpoint into the M phase
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
 The peaks of MPF activity corresponds to the peaks of cyclin
concentration.
 Cyclin level rises during the S and G2 , then falls during M
phase.

52. Figure 12.17b
Molecular mechanisms that help regulate the cell cycle
S
G
1
1. Synthesis of cyclin
begins in S and
continue through G2.
Cdk
Degraded
cyclin
Cyclin is
degraded
M
G2
Cdk
G2
checkpoint
MPF
Cyclin

53. Figure 12.17b
Molecular mechanisms that help regulate the cell cycle
G
1
S
Cdk
M
G2
Degraded
cyclin
G2
checkpoint
Cyclin is
degraded
MPF
Cdk
Cyclin
2. Cyclin combines with Cdk, producing MPF.
MPF accumulate, the cell passes the G2
checkpoint and begins mitosis.

54. Molecular mechanisms that help regulate the cell cycle
1
S
G
Figure 12.17b
Cdk
Degraded
cyclin
Cyclin is
degraded
M
G2
G2
checkpoint
MPF
Cdk
Cyclin
3. MPF phosphorylates various proteins.
MPF’s activity peaks during metaphase.

55. Molecular mechanisms that help regulate the cell cycle
S
G
1
Figure 12.17b
Cdk
Degraded
cyclin
Cyclin is
degraded
M
G2
G2
checkpoint
MPF
4. Anaphase, cyclin component of MPF is
degraded, terminating M phase.
The cell enters G1.
Cdk
Cyclin

56. Figure 12.17b
Molecular mechanisms that help regulate the cell cycle
5. G1, degradation of
cyclin continues.
Cdk component of MPF is
recycled.
G
1
S
Cdk
Degraded
cyclin
Cyclin is
degraded
M
G2
G2
checkpoint
MPF
Cdk
Cyclin

57. Figure 12.17b
Molecular mechanisms that help regulate the cell cycle
1. Synthesis of cyclin begins in S
and continue through G2.
5. G1, degradation of cyclin
continues.
Cdk component of MPF is
recycled.
G
1
S
Cdk
Degraded
cyclin
Cyclin is
degraded
4. Anaphase, cyclin
component of MPF is
degraded, terminating M
phase.
The cell enters G1.
M
G2
G2
checkpoint
MPF
3. MPF phosphorylates
various proteins.
MPF’s activity peaks during
metaphase.
Cdk
Cyclin
2.Cyclin combines with Cdk,
producing MPF.
MPF accumulate, the cell passes
the G2 checkpoint and begins
mitosis.

58. 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
(connective tissue) cells in culture
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59. Figure 12.18
Scalpels
1 A sample of human
connective tissue is
cut up into small
pieces.
2 Enzymes digest
the extracellular
matrix, resulting in
a suspension of
free fibroblasts.
Petri
dish
3 Cells are transferred to
culture vessels.
Without PDGF
4 PDGF is added
to half the
vessels.
With PDGF
10 µm

60. • A clear example of external signals is densitydependent 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
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61. Figure 12.19
Anchorage dependence, cells anchor to dish surface
and divide.
Density-dependent inhibition, when cell have formed
a single layer, crowded cells stop dividing
Density-dependent inhibition
20 µm
(a) Normal mammalian cells

62. Figure 12.19
20 µm
(b) Cancer cells
Cancer cells, exhibit neither density dependent
inhibition nor anchorage dependence.

63. 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
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64. • 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, not a serious
problem
• Malignant tumors invade surrounding tissues and
can metastasize, exporting cancer cells to other
parts of the body, where they may form additional
tumors
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65. Figure 12.20
Tumor
Lymph
vessel
Blood
vessel
Glandular
tissue
Cancer
cell
1 A tumor grows
from a single
cancer cell.
Metastatic
tumor
2 Cancer
cells invade
neighboring
tissue.
3 Cancer cells spread
through lymph and
blood vessels to
other parts of the
body.
4 Cancer cells
may survive
and establish
a new tumor
in another part
of the body.

66. • Recent advances in understanding the cell
cycle and cell cycle signaling have led to
advances in cancer treatment
• Tx: cell cycle specific inhibitors, monoclonal
antibodies, etc
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