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Cell Cycle
M
What is the cell cycle?
 All cells are derived from pre-existing cells
 Cell cycle: defined as ordered sequences of events that
occurs in the cell in preparation of cell division.
 The Cell cycle has two basic Function :
 Copying cellular components and DNA duplication
 Dividing the cell so that components are distributed evenly to
the daughter cells
 The alternating “growth” and “division” activities of the
cell is called the “cell cycle”.
 Cell division is an integral part of the cell cycle.
Cell cycle
3
Parent Cell
Two
identical
daughter
cells
•In unicellular organisms, division of one cell
reproduces the entire organism (reproduction)
•Multicellular organisms depend on cell division for
• Growth (increase in numbers) and maintained
and repaired (adults renewal e.g. liver, skin).
Why the cell division occur?
Are all cells divide?
•NO some cell can’t divide e.g eye lens, nerve cell,
heart cells. Theses cells maintained and repaired by
replacing the intracellular component.
Types of Cell Reproduction
5
 Asexual reproduction
involves a (smatic cell) single cell dividing to make 2 new,
identical daughter cells (eg.Mitosis)
 Sexual reproduction
 involves two cells (egg & sperm) joining to make a new
cell (zygote) that is NOT identical to the original cells (
e.g.Meiosis )
 All diploid chromosomes is homologous except six
chromosome in male (y from father & x from mother)
Diploid (46
chr)
Haploid (23 chr)
 The “growth” activity corresponds to “Interphase”.
cell growth and copying of chromosomes in
preparation for cell division
 The division activity corresponds to “M phase”.
What is the cell cycle basic function?
(mitosis andcytokinesis)
Interphase M Interphase M Interphase
G1 S G2 M G1 S G2 M G1 S G2
Figure 12.6
INTERPHASE
G1
G2
S
(DNA synthesis)
 Interphase (about 90% of the cell cycle) is span
between cell division can be divided into subphases
 G1 phase (“first gap”) the cell size increased
 S phase (“synthesis”) chromosomes are duplicated
(longest phase)
 G2 phase (“second gap”) cell prepared to divide
© 2011 Pearson Education, Inc.
Interphase
Interphase
Interphase
G1 & G2 gap:
-The cell grows and mass protein and organelles are
duplicated.
-The cell monitor the internal and external
environment to ensure the condition suitable and
prepare for S and M.
-In unfavorable extracellular condition the cell delay
progression through G1.
-The cell may enter in G0 (resting state) it may stay in
until die or until the condition become favorable and
cell can row and divide.
Interphase
 In yeast “Start” is at the end of G1; at this point the cell is
committed to DNA synthesis.
 In mammals, this is called the “restriction point”. This point
late in G1 is a “checkpoint”; a cell will exit the cell cycle if
certain requirements to proceed to synthesis are not met.
 After passing this point even the signal stimulating cell growth
removed the DNA will synthesis.
 A second restriction point occurs in G2 before entry into
mitosis.
Interphase: G1
 Events during G1
 1 st stage of Cell growth after cell division
 Preparation of chromosomes for replication
 Duplication of cellular components (cytoplasm and organel)
 Cell carries on its normal metabolic activities
 G1 checkpoint (or restriction point); cell commits to division or
exits from cell cycle
S- phase
 The instructions for making cell parts are
encoded in the DNA, so each new cell must
get a complete set of the DNA molecules
 DNA must be copied or replicated before
cell division
 Each new cell will then have an identical
copy of the DNA
13
Original DNA
strand
Two new, identical
DNA strands
 Duplicated chromosomes
are called chromatids
 & are held together by
the centromere
14
Called Sister Chromatids
S- phase
 DNA replication
 Duplication of the centrosome
 The centrosome is located near the nucleus of the cell and
contains the microtubule organizing center MTOC in animal
cells. It contains two centrioles surrounding by loose
collection of protein that migrate to the poles before cell
division and serve to organize the spindle.
S- phase
Interphase: G2
 2 nd Cell growth stage
 Occurs after DNA has been copied
 All cell structures needed for division are made (e.g.
centrioles)
 Both organelles & proteins are synthesized
 Checkpoint (restriction point) for entry into M phase
Mitosis
17
Daughter
Cells
DNA Copied
Cells
Mature
Cells prepare for Division
Cell Divides into Identical cells
 Mitosis (cell division) is highly regulated process include
(karyokinesis) nucleus division and cytoplasm division
cytokinesis.
 Only occurs in eukaryotes
 Doesn’t occur in some cells such as brain cells
 Mitosis stage conventionally divided into five phases
 Prophase
 Prometaphase
 Metaphase
 Anaphase
 Telophase
 Cytokinesis overlaps the latter stages of mitosis
© 2011 Pearson Education, Inc.
Mitosis phase
PROPHASE
 the first phase in mitosis and longest phase of mitosis.
 THREE THINGS TO LOOK FOR:
1.chromosomes can be visible under light microscope as two
chromatids, in the shape of an “X” (chromatin condenses to
form chromosomes)
2.Nuclear envelope dissolves ( begin disagrregate)
3.Centrioles are present with some spindle fibers and the sister
chromatids are attached by their kinetochores to microtubules
from opposite poles
prophase
•kinetochore is a protein strucutre on
chromatide where microtubules will
bind to it in cell division to pull the
two sister chromatide a part
•each sister chromatid has its own
kinetochore (arise from centromer)
•sister chromatids become attached
by their kinetochores to microtubules
from opposite poles
•Used in cell division (mitosis &
miosis)
Spindle Fiber attached to
Chromosome
21
Kinetochore Fiber
Chromosome
prometaphase
 a system of
microtubules, called
the mitotic spindle,
organizes between the
two poles (opposite
ends) of the cell
 each pole has a
microtubule organizing
center (MTOC)
 in animals and some
other eukaryotes,
centrioles are found in
the MTOC
Late Prophase (prometaphase)
23
 Nuclear membrane & nucleolus are broken
down
 Chromosomes continue condensing & are
clearly visible
 Spindle fibers called kinetochores attach to
the centromere of each chromosome
 Spindle finishes forming between the poles of
the cell
Review of Prophase
24
What the cell looks like
What’s happening
METAPHASE
1.Chromosomes chromosomes are highly condensed line
up in the middle (meta phase plate)
2.Nuclear envelope is gone (no nucleus)
3.Spindle fibers (on opposite poles) are stretching
towards the chromosomes
4- the mitosis checkpoint appears to be here; progress
past metaphase is typically prevented until the
kinetochores are all attached to microtubules
Sketch The Spindle
26
Review of Metaphase
27
What the cell looks like
What’s occurring
Anaphase
 Occurs rapidly
 Sister chromatids are
pulled apart to
opposite poles of the
cell by kinetochore
fibers
 the protein
tethers at the
centromere
between the
chromatids are
broken
 each former sister
chromatid can
now be called a
chromosome
(daughter)
28
CHROMOSOME STRUCTURE
CENTROMERE
CHROMATID
CHROMATID
Anaphase Review
30
What the cell
looks like
What’s
occurring
Telophase
31
 Sister chromatids at opposite poles
 Spindle disassembles
 Nuclear envelope forms around each set of
sister chromatids and chromosome
condensed
 Nucleolus reappears
 CYTOKINESIS occurs (furrow)
 Chromosomes reappear as chromatin
Mitosis: telophase
 prophase is essentially
reversed
 the mitotic spindle is
disintegrated
 the chromosomes decondense
 nuclear membranes reform
around the genetic material to
form two nuclei
 each has an identical copy of
the genetic information
 nucleoli reappear, and
interphase cellular functions
resume
*
Comparison of Anaphase & Telophase
33
PARENT CELLS
DAUGHTER
CELLS
Cell Division in Prokaryotes
Prokaryotes such as
bacteria divide into 2
identical cells by the
process of binary
fission
Single chromosome
makes a copy of
itself
Cell wall forms
between the
chromosomes dividing
the cell
35
Parent cell
2 identical daughter cells
Chromosome
doubles
Cell splits
What is the Cell Cycle?
 Parent cells are diploid and make 2 daughter cells that
are also diploid with their own new nuclei.
 Diploid means 2 of each chromosome: 2 (n)= 2
(23) = 46 chromosomes
 It happens in all of your somatic(body) cells in order to
get the same DNA inside each cell. (your reproductive
cells do something different)
I P M A T C
I Peed on the MAT, see?
Figure 12.5-3
Chromosomes
Chromosomal
DNA molecules
Centromere
Chromosome
arm
Chromosome duplication
(including DNA replication)
and condensation
Sister
chromatids
Separation of sister
chromatids into
two chromosomes
1
2
3
cytokinesis
 Means division of the
cytoplasm
 divides the cell into two
daughter cells
(cytoplasm, organelles
 cytokinesis usually
begins in telophase and
ends shortly thereafter
Cytokinesis
40
Cleavage furrow
in animal cell
Cell plate in
animal cell
Daughter Cells of Mitosis
41
 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 (G1
of Interphase)
 Ready to enter in new cell cycle
Identical Daughter Cells
42
Chromosome number the same, but cells
smaller than parent cell
What is
the 2n or
diploid
number?
2
Review
of
Mitosis
44
Draw & Learn these Stages
45
Draw & Learn these Stages
46
Name the Mitotic Stages:
47
Interphase
Prophase
Metaphase
Anaphase
Telophase
Name this?
Name this?
Uncontrolled Mitosis
If mitosis is not
controlled, unlimited
cell division occurs
causing cancerous
tumors
Oncogenes are special
proteins that increase
the chance that a
normal cell develops
into a tumor cell
48
Cancer cells
controlled Mitosis
 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.
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.
G1 checkpoint
G1
G2
G2 checkpoint
M checkpoint
M
S
Control
system
Figure 12.15
 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
G1 checkpoint
G1 G1
G0
(a) Cell receives a go-ahead
signal.
(b) Cell does not receive a
go-ahead signal.
Eukaryotic Cell Cycle
cyclins and cyclin-dependent protein kinases (Cdks)
cytokinins; growth factors; suppressors; cancer cells
Cell Cycle Checkpoints
 The decision to proceed from one part of the cell cycle to
another depends on a variety of factors
 Growth
 DNA replication
 DNA integrity
 Cellular integrity
The mechanisms that the cell has to monitor these factors act at
“checkpoints”
Generally, the feedback from checkpoints is through negative
regulation—sending a signal to stop the progression of the cell cycle
rather than dialing back a positive signal.
Schematic of Cell Cycle Checkpoints
Cell Cycle Checkpoints
 G1 (Restriction) Checkpoint
 DNA Replication Checkpoint (end of G2)
 Cell will not proceed with mitosis if DNA replication is not
complete
 Cells with mutations in this checkpoint pathway or cultured
mammalian cells treated with caffeine will proceed through
mitosis with unreplicated DNA.
Cell Cycle Arrest
 Cells have “checkpoints” where they “proof-read” DNA for damage
before continuing to cycle. This ensures faithful chromosome replication
and maintains genomic integrity.
 Irradiation causes cells to arrest at these checkpoints
 Cells tend to arrest at
• G1 - especially if they have wt p53. This may lead to apoptosis
• Intra S phase - initiation and elongation stages of DNA replication
are affected by p53 independent mechanisms
• G2 - most cells arrest here - allows chromatid repair prior to
segregation in M
• M phase - block in anaphase until all sister chromatids
have aligned properly on the spindle - Monitors spindle
integrity for cytokinesis
Cell Cycle Checkpoints
 Growth checkpoints
 In budding yeasts, division produces a small daughter cell and
a large mother cell. The daughter cell spends a longer time
growing in G1 before it can divide again. There is a minimum
size that must be reached before S phase can begin.
 In animal cells, external growth factors play a major role in
providing signals about cell growth and differentiation and
regulating the cell cycle.
Cell Cycle Checkpoints
 Spindle-attachment checkpoint
 Before anaphase (separation of chromosomes) there is a
checkpoint to ensure the chromatids are correctly attached to
the mitotic spindle
 The kinetochore (where the chromatids attach to the spindle)
is the structure that is monitored
Cell Cycle Checkpoints
 Exiting Mitosis
 Degradation of the M phase cyclin/cdk complex (aka MPF) is
required to proceed with the final activities of mitosis (spindle
disassembly and formation of the nuclear envelopes).
 This degradation is accomplished by ubiquitinylation of the
complex.
 The cdc20-APC complex is responsible for signaling the
degradation and exit from mitosis.
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.
cell cycle and control checkpoints throght  cyclin cdk complex
cell cycle and control checkpoints throght  cyclin cdk complex
cell cycle and control checkpoints throght  cyclin cdk complex
cell cycle and control checkpoints throght  cyclin cdk complex

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cell cycle and control checkpoints throght cyclin cdk complex

  • 2. What is the cell cycle?  All cells are derived from pre-existing cells  Cell cycle: defined as ordered sequences of events that occurs in the cell in preparation of cell division.  The Cell cycle has two basic Function :  Copying cellular components and DNA duplication  Dividing the cell so that components are distributed evenly to the daughter cells  The alternating “growth” and “division” activities of the cell is called the “cell cycle”.  Cell division is an integral part of the cell cycle.
  • 4. •In unicellular organisms, division of one cell reproduces the entire organism (reproduction) •Multicellular organisms depend on cell division for • Growth (increase in numbers) and maintained and repaired (adults renewal e.g. liver, skin). Why the cell division occur? Are all cells divide? •NO some cell can’t divide e.g eye lens, nerve cell, heart cells. Theses cells maintained and repaired by replacing the intracellular component.
  • 5. Types of Cell Reproduction 5  Asexual reproduction involves a (smatic cell) single cell dividing to make 2 new, identical daughter cells (eg.Mitosis)  Sexual reproduction  involves two cells (egg & sperm) joining to make a new cell (zygote) that is NOT identical to the original cells ( e.g.Meiosis )  All diploid chromosomes is homologous except six chromosome in male (y from father & x from mother) Diploid (46 chr) Haploid (23 chr)
  • 6.  The “growth” activity corresponds to “Interphase”. cell growth and copying of chromosomes in preparation for cell division  The division activity corresponds to “M phase”. What is the cell cycle basic function? (mitosis andcytokinesis) Interphase M Interphase M Interphase G1 S G2 M G1 S G2 M G1 S G2
  • 8.  Interphase (about 90% of the cell cycle) is span between cell division can be divided into subphases  G1 phase (“first gap”) the cell size increased  S phase (“synthesis”) chromosomes are duplicated (longest phase)  G2 phase (“second gap”) cell prepared to divide © 2011 Pearson Education, Inc. Interphase
  • 10. Interphase G1 & G2 gap: -The cell grows and mass protein and organelles are duplicated. -The cell monitor the internal and external environment to ensure the condition suitable and prepare for S and M. -In unfavorable extracellular condition the cell delay progression through G1. -The cell may enter in G0 (resting state) it may stay in until die or until the condition become favorable and cell can row and divide.
  • 11. Interphase  In yeast “Start” is at the end of G1; at this point the cell is committed to DNA synthesis.  In mammals, this is called the “restriction point”. This point late in G1 is a “checkpoint”; a cell will exit the cell cycle if certain requirements to proceed to synthesis are not met.  After passing this point even the signal stimulating cell growth removed the DNA will synthesis.  A second restriction point occurs in G2 before entry into mitosis.
  • 12. Interphase: G1  Events during G1  1 st stage of Cell growth after cell division  Preparation of chromosomes for replication  Duplication of cellular components (cytoplasm and organel)  Cell carries on its normal metabolic activities  G1 checkpoint (or restriction point); cell commits to division or exits from cell cycle
  • 13. S- phase  The instructions for making cell parts are encoded in the DNA, so each new cell must get a complete set of the DNA molecules  DNA must be copied or replicated before cell division  Each new cell will then have an identical copy of the DNA 13 Original DNA strand Two new, identical DNA strands
  • 14.  Duplicated chromosomes are called chromatids  & are held together by the centromere 14 Called Sister Chromatids S- phase
  • 15.  DNA replication  Duplication of the centrosome  The centrosome is located near the nucleus of the cell and contains the microtubule organizing center MTOC in animal cells. It contains two centrioles surrounding by loose collection of protein that migrate to the poles before cell division and serve to organize the spindle. S- phase
  • 16. Interphase: G2  2 nd Cell growth stage  Occurs after DNA has been copied  All cell structures needed for division are made (e.g. centrioles)  Both organelles & proteins are synthesized  Checkpoint (restriction point) for entry into M phase
  • 17. Mitosis 17 Daughter Cells DNA Copied Cells Mature Cells prepare for Division Cell Divides into Identical cells
  • 18.  Mitosis (cell division) is highly regulated process include (karyokinesis) nucleus division and cytoplasm division cytokinesis.  Only occurs in eukaryotes  Doesn’t occur in some cells such as brain cells  Mitosis stage conventionally divided into five phases  Prophase  Prometaphase  Metaphase  Anaphase  Telophase  Cytokinesis overlaps the latter stages of mitosis © 2011 Pearson Education, Inc. Mitosis phase
  • 19. PROPHASE  the first phase in mitosis and longest phase of mitosis.  THREE THINGS TO LOOK FOR: 1.chromosomes can be visible under light microscope as two chromatids, in the shape of an “X” (chromatin condenses to form chromosomes) 2.Nuclear envelope dissolves ( begin disagrregate) 3.Centrioles are present with some spindle fibers and the sister chromatids are attached by their kinetochores to microtubules from opposite poles
  • 20. prophase •kinetochore is a protein strucutre on chromatide where microtubules will bind to it in cell division to pull the two sister chromatide a part •each sister chromatid has its own kinetochore (arise from centromer) •sister chromatids become attached by their kinetochores to microtubules from opposite poles •Used in cell division (mitosis & miosis)
  • 21. Spindle Fiber attached to Chromosome 21 Kinetochore Fiber Chromosome
  • 22. prometaphase  a system of microtubules, called the mitotic spindle, organizes between the two poles (opposite ends) of the cell  each pole has a microtubule organizing center (MTOC)  in animals and some other eukaryotes, centrioles are found in the MTOC
  • 23. Late Prophase (prometaphase) 23  Nuclear membrane & nucleolus are broken down  Chromosomes continue condensing & are clearly visible  Spindle fibers called kinetochores attach to the centromere of each chromosome  Spindle finishes forming between the poles of the cell
  • 24. Review of Prophase 24 What the cell looks like What’s happening
  • 25. METAPHASE 1.Chromosomes chromosomes are highly condensed line up in the middle (meta phase plate) 2.Nuclear envelope is gone (no nucleus) 3.Spindle fibers (on opposite poles) are stretching towards the chromosomes 4- the mitosis checkpoint appears to be here; progress past metaphase is typically prevented until the kinetochores are all attached to microtubules
  • 27. Review of Metaphase 27 What the cell looks like What’s occurring
  • 28. Anaphase  Occurs rapidly  Sister chromatids are pulled apart to opposite poles of the cell by kinetochore fibers  the protein tethers at the centromere between the chromatids are broken  each former sister chromatid can now be called a chromosome (daughter) 28
  • 30. Anaphase Review 30 What the cell looks like What’s occurring
  • 31. Telophase 31  Sister chromatids at opposite poles  Spindle disassembles  Nuclear envelope forms around each set of sister chromatids and chromosome condensed  Nucleolus reappears  CYTOKINESIS occurs (furrow)  Chromosomes reappear as chromatin
  • 32. Mitosis: telophase  prophase is essentially reversed  the mitotic spindle is disintegrated  the chromosomes decondense  nuclear membranes reform around the genetic material to form two nuclei  each has an identical copy of the genetic information  nucleoli reappear, and interphase cellular functions resume *
  • 33. Comparison of Anaphase & Telophase 33
  • 35. Cell Division in Prokaryotes Prokaryotes such as bacteria divide into 2 identical cells by the process of binary fission Single chromosome makes a copy of itself Cell wall forms between the chromosomes dividing the cell 35 Parent cell 2 identical daughter cells Chromosome doubles Cell splits
  • 36. What is the Cell Cycle?  Parent cells are diploid and make 2 daughter cells that are also diploid with their own new nuclei.  Diploid means 2 of each chromosome: 2 (n)= 2 (23) = 46 chromosomes  It happens in all of your somatic(body) cells in order to get the same DNA inside each cell. (your reproductive cells do something different) I P M A T C I Peed on the MAT, see?
  • 37.
  • 38. Figure 12.5-3 Chromosomes Chromosomal DNA molecules Centromere Chromosome arm Chromosome duplication (including DNA replication) and condensation Sister chromatids Separation of sister chromatids into two chromosomes 1 2 3
  • 39. cytokinesis  Means division of the cytoplasm  divides the cell into two daughter cells (cytoplasm, organelles  cytokinesis usually begins in telophase and ends shortly thereafter
  • 40. Cytokinesis 40 Cleavage furrow in animal cell Cell plate in animal cell
  • 41. Daughter Cells of Mitosis 41  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 (G1 of Interphase)  Ready to enter in new cell cycle
  • 42. Identical Daughter Cells 42 Chromosome number the same, but cells smaller than parent cell What is the 2n or diploid number? 2
  • 43.
  • 45. Draw & Learn these Stages 45
  • 46. Draw & Learn these Stages 46
  • 47. Name the Mitotic Stages: 47 Interphase Prophase Metaphase Anaphase Telophase Name this? Name this?
  • 48. Uncontrolled Mitosis If mitosis is not controlled, unlimited cell division occurs causing cancerous tumors Oncogenes are special proteins that increase the chance that a normal cell develops into a tumor cell 48 Cancer cells
  • 49. controlled Mitosis  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.
  • 50. 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.
  • 51. G1 checkpoint G1 G2 G2 checkpoint M checkpoint M S Control system Figure 12.15
  • 52.  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.
  • 53. Figure 12.16 G1 checkpoint G1 G1 G0 (a) Cell receives a go-ahead signal. (b) Cell does not receive a go-ahead signal.
  • 54. Eukaryotic Cell Cycle cyclins and cyclin-dependent protein kinases (Cdks) cytokinins; growth factors; suppressors; cancer cells
  • 55. Cell Cycle Checkpoints  The decision to proceed from one part of the cell cycle to another depends on a variety of factors  Growth  DNA replication  DNA integrity  Cellular integrity The mechanisms that the cell has to monitor these factors act at “checkpoints” Generally, the feedback from checkpoints is through negative regulation—sending a signal to stop the progression of the cell cycle rather than dialing back a positive signal. Schematic of Cell Cycle Checkpoints
  • 56. Cell Cycle Checkpoints  G1 (Restriction) Checkpoint  DNA Replication Checkpoint (end of G2)  Cell will not proceed with mitosis if DNA replication is not complete  Cells with mutations in this checkpoint pathway or cultured mammalian cells treated with caffeine will proceed through mitosis with unreplicated DNA.
  • 57. Cell Cycle Arrest  Cells have “checkpoints” where they “proof-read” DNA for damage before continuing to cycle. This ensures faithful chromosome replication and maintains genomic integrity.  Irradiation causes cells to arrest at these checkpoints  Cells tend to arrest at • G1 - especially if they have wt p53. This may lead to apoptosis • Intra S phase - initiation and elongation stages of DNA replication are affected by p53 independent mechanisms • G2 - most cells arrest here - allows chromatid repair prior to segregation in M • M phase - block in anaphase until all sister chromatids have aligned properly on the spindle - Monitors spindle integrity for cytokinesis
  • 58. Cell Cycle Checkpoints  Growth checkpoints  In budding yeasts, division produces a small daughter cell and a large mother cell. The daughter cell spends a longer time growing in G1 before it can divide again. There is a minimum size that must be reached before S phase can begin.  In animal cells, external growth factors play a major role in providing signals about cell growth and differentiation and regulating the cell cycle.
  • 59. Cell Cycle Checkpoints  Spindle-attachment checkpoint  Before anaphase (separation of chromosomes) there is a checkpoint to ensure the chromatids are correctly attached to the mitotic spindle  The kinetochore (where the chromatids attach to the spindle) is the structure that is monitored
  • 60. Cell Cycle Checkpoints  Exiting Mitosis  Degradation of the M phase cyclin/cdk complex (aka MPF) is required to proceed with the final activities of mitosis (spindle disassembly and formation of the nuclear envelopes).  This degradation is accomplished by ubiquitinylation of the complex.  The cdc20-APC complex is responsible for signaling the degradation and exit from mitosis.
  • 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.