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The Cell Cycle
Dr. Jorge Rodríguez
Overview: The Key Roles of Cell Division
• The ability of organisms to produce more of their
own kind best distinguishes l...
Cell division plays several important roles
in life
• In unicellular organisms (proka- or eukaryotes),
division of one cel...
Figure 12.2

100 µm

(a) Reproduction
Amoeba, dividing into two cells

200 µm
(b) Growth and
development
Sand dollar, embr...
Most cell division results in genetically
identical daughter cells
• Most cell division results in daughter cells with
ide...
Cellular Organization of the Genetic
Material
• All the DNA in a cell constitutes the cell’s genome
• A genome can consist...
Figure 12.3

20 µm
DNA molecules in a cell are packaged into chromosomes
Figure 6.9a

Nucleus

Nucleolus
Chromatin
Nuclear envelope:
Inner membrane
Outer membrane
Nuclear pore

Rough ER
Pore
comp...
DNA molecule carries several hundreds to a few
thousand genes
The associated proteins mantain the structure of the
chromosome and help control the activities of the genes
Eukaryotic ch...
• Every eukaryotic species has
a characteristic number of
chromosomes in each cell
nucleus
• Somatic cells (body cells,
no...
Distribution of Chromosomes During Eukaryotic
Cell Division
• In preparation for cell division, DNA is replicated and the
...
• The centromere is the narrow “waist” of the duplicated
chromosome, where the two chromatids are most closely
attached
• ...
• During cell division, the two sister chromatids of
each duplicated chromosome separate and move
into two nuclei
• Once s...
Figure 12.5-3

Chromosomes
1

Chromosomal
DNA molecules

Centromere

Chromosome
arm
Chromosome duplication
(including DNA ...
• Eukaryotic cell division consists of
– Mitosis, the division of the genetic material in the
nucleus
– Cytokinesis, the d...
The mitotic phase alternates with
interphase in the cell cycle
• In 1882, the German anatomist Walther Flemming
developed ...
Phases of the Cell Cycle
• The cell cycle consists of
– Mitotic (M) phase (mitosis and cytokinesis)
– Interphase (cell gro...
• Interphase (about 90% of the cell cycle) can be
divided into subphases
– G1 phase (“first gap”)
– S phase (“synthesis”)
...
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...
• Mitosis is conventionally divided into five phases
–
–
–
–
–

Prophase
Prometaphase
Metaphase
Anaphase
Telophase

• Cyto...
Figure 12.7a

G2 of Interphase

Centrosomes
(with centriole
pairs)

Prometaphase

Prophase

Fragments
Chromatin Early mito...
Figure 12.7b

Metaphase

Anaphase

Metaphase
plate

Spindle

Telophase and Cytokinesis
Cleavage
furrow

Centrosome at
one ...
Figure 12.UN01

INTERPHASE

G1

S

Cytokinesis
G2

Mitosis
MITOTIC (M) PHASE

Prophase
Telophase and
Cytokinesis
Prometaph...
Figure 12.7a

The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)

Chromatin
(duplicate...
Figure 12.7a

The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)

Chromatin
(duplicate...
Figure 12.7a

The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)

Chromatin
(duplicate...
Figure 12.7a

The Mitotic Spindle: A Closer Look
G2 of Interphase
Centrosomes
(with centriole
pairs)

Chromatin
(duplicate...
Figure 12.7b

Metaphase

Anaphase

Metaphase
plate

Spindle

Centrosome at
one spindle pole

Telophase and Cytokinesis
Cle...
Figure 12.8

Aster

Centrosome

Sister
chromatids

Metaphase
plate
(imaginary)

Microtubules

Chromosomes
Kinetochores

Ce...
Figure 12.UN04
Figure 12.7b

Metaphase

Anaphase

Metaphase
plate

Spindle

•
•
•

Centrosome at
one spindle pole

Telophase and Cytokine...
Figure 12.7b

Metaphase

Anaphase

Metaphase
plate

Spindle

•
•
•
•

Centrosome at
one spindle pole

Telophase and Cytoki...
Cytokinesis: A Closer Look
• In animal cells, cytokinesis occurs by a process
known as cleavage, forming a cleavage furrow...
Figure 12.10a

(a) Cleavage of an animal cell (SEM)

Cleavage furrow
(old metaphase plate)

100 µm

Contractile ring of mi...
(b) Cell plate formation in a plant cell (TEM)

• No cleavage furrow formed.
• Telophase, vesicles from
Golgi move to the ...
Binary Fission in Bacteria
• Prokaryotes (bacteria and archaea) reproduce by
a type of cell division called binary fission...
Figure 12.12-1

Origin of
replication
E. coli cell
1 Chromosome
replication
begins.

Cell wall
Plasma membrane
Bacterial c...
Figure 12.12-2

Origin of
replication
E. coli cell

1 Chromosome
replication
begins.
2 Replication
continues.

Cell wall
P...
Figure 12.12-3

Origin of
replication
E. coli cell

1 Chromosome
replication
begins.
2 Replication
continues.

Cell wall
P...
Figure 12.12-4

Origin of
replication
E. coli cell

1 Chromosome
replication
begins.
2 Replication
continues.

3 Replicati...
The eukaryotic cell cycle is regulated by a
molecular control system
• The frequency of cell division varies with the type...
Evidence for Cytoplasmic Signals
• The cell cycle appears to be driven by specific
chemical signals present in the cytopla...
Figure 12.14

EXPERIMENT
Experiment 1

S

G1

S

S

Experiment 2

M

G1

RESULTS

When a cell in the S
phase was fused
wit...
The Cell Cycle Control System
• The sequential events of the cell cycle are directed
by a distinct cell cycle control syst...
Figure 12.15

G1 checkpoint

Control
system

G1

M

M checkpoint

S

G2

G2 checkpoint

Three major checkpoints:
G1, G2, M...
Figure 12.16

G0
G1 checkpoint

G1
(a) Cell receives a go-ahead
signal.

G1
(b) Cell does not receive a
go-ahead signal.

...
The Cell Cycle Clock: Cyclins and CyclinDependent Kinases
• Two types of regulatory proteins are involved in
cell cycle co...
Figure 12.17a

MPF (maturation-promoting factor) is a cyclin-Cdk
complex that triggers a cell’s passage past the G2
checkp...
Figure 12.17b

Molecular mechanisms that help regulate the cell cycle

S

G

1

1. Synthesis of cyclin
begins in S and
con...
Figure 12.17b

Molecular mechanisms that help regulate the cell cycle

G

1

S

Cdk
M
G2

Degraded
cyclin

G2
checkpoint

...
Molecular mechanisms that help regulate the cell cycle

1

S

G

Figure 12.17b

Cdk
Degraded
cyclin
Cyclin is
degraded

M
...
Molecular mechanisms that help regulate the cell cycle

S

G

1

Figure 12.17b

Cdk
Degraded
cyclin
Cyclin is
degraded

M
...
Figure 12.17b

Molecular mechanisms that help regulate the cell cycle

5. G1, degradation of
cyclin continues.
Cdk compone...
Figure 12.17b

Molecular mechanisms that help regulate the cell cycle
1. Synthesis of cyclin begins in S
and continue thro...
Stop and Go Signs: Internal and External
Signals at the Checkpoints
• An example of an internal signal is that
kinetochore...
Figure 12.18

Scalpels

1 A sample of human
connective tissue is
cut up into small
pieces.

2 Enzymes digest
the extracell...
• A clear example of external signals is densitydependent inhibition, in which crowded cells stop
dividing
• Most animal c...
Figure 12.19

Anchorage dependence, cells anchor to dish surface
and divide.

Density-dependent inhibition, when cell have...
Figure 12.19

20 µm
(b) Cancer cells

Cancer cells, exhibit neither density dependent
inhibition nor anchorage dependence.
Loss of Cell Cycle Controls in Cancer Cells
• Cancer cells do not respond normally to the body’s
control mechanisms
• Canc...
• A normal cell is converted to a cancerous cell by a
process called transformation
• Cancer cells that are not eliminated...
Figure 12.20

Tumor

Lymph
vessel
Blood
vessel

Glandular
tissue

Cancer
cell

1 A tumor grows

from a single
cancer cell....
• Recent advances in understanding the cell
cycle and cell cycle signaling have led to
advances in cancer treatment
• Tx: ...
The Cell Cycle
The Cell Cycle
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The Cell Cycle

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The Cell Cycle

  1. 1. The Cell Cycle Dr. Jorge Rodríguez
  2. 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 © 2011 Pearson Education, Inc.
  3. 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. 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. 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. 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. 7. Figure 12.3 20 µm DNA molecules in a cell are packaged into chromosomes
  8. 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. 9. DNA molecule carries several hundreds to a few thousand genes
  10. 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. 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. 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 © 2011 Pearson Education, Inc. 0.5 µm
  13. 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 © 2011 Pearson Education, Inc. 0.5 µm
  14. 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. 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. 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 © 2011 Pearson Education, Inc.
  17. 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 © 2011 Pearson Education, Inc.
  18. 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. 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. 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. 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. 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. 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. 24. Figure 12.UN01 INTERPHASE G1 S Cytokinesis G2 Mitosis MITOTIC (M) PHASE Prophase Telophase and Cytokinesis Prometaphase Anaphase Metaphase
  25. 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
  26. 26. 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
  27. 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 An aster (a radial array of short microtubules) extends from each centrosome The spindle includes the centrosomes, the spindle microtubules, and the asters
  28. 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 • 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
  29. 29. 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
  30. 30. 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
  31. 31. Figure 12.UN04
  32. 32. 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
  33. 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, 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
  34. 34. 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 © 2011 Pearson Education, Inc.
  35. 35. 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)
  36. 36. (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
  37. 37. 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 © 2011 Pearson Education, Inc.
  38. 38. 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).
  39. 39. 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.
  40. 40. 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.
  41. 41. 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
  42. 42. 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 © 2011 Pearson Education, Inc.
  43. 43. 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.
  44. 44. 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.
  45. 45. 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.
  46. 46. Figure 12.15 G1 checkpoint Control system G1 M M checkpoint S G2 G2 checkpoint Three major checkpoints: G1, G2, M phases
  47. 47. 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
  48. 48. 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 © 2011 Pearson Education, Inc.
  49. 49. 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.
  50. 50. 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
  51. 51. 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.
  52. 52. 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.
  53. 53. 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
  54. 54. 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
  55. 55. 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.
  56. 56. 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 © 2011 Pearson Education, Inc.
  57. 57. 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
  58. 58. • 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 © 2011 Pearson Education, Inc.
  59. 59. 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
  60. 60. Figure 12.19 20 µm (b) Cancer cells Cancer cells, exhibit neither density dependent inhibition nor anchorage dependence.
  61. 61. 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.
  62. 62. • 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 © 2011 Pearson Education, Inc.
  63. 63. 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.
  64. 64. • 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 © 2011 Pearson Education, Inc.

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