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Cell Cycle- Interphase & Mitosis (2) atf

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CELL CYCLE: INTERPHASE & MITOSIS
Cell Biology | Cell Cycle: Interphase & Mitosis
Medical Editor: Gerard Jude Loyola
OUTLINE
I) CELL CYCLE
II) INTERPHASE
III) MITOSIS
IV) MITOSIS MODELS
V) WRAPPING UP
VI) SUPPLEMENTARY IMAGES
VII) APPENDIX
VIII) REVIEW QUESTIONS
I) CELL CYCLE
Figure 1. Overview of the interphase and mitosis.
Cell cycle
o Interphase and mitosis
o Series of phases and steps that a cell goes to
replicate itself
 Turning one cell into two
o Also important to control cell growth
 Cell cycle regulation: proto-oncogenes, tumor
suppressor genes, DNA repair enzymes
Cell Cycle: Interphase & Mitosis
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Cello
o Basic unit of all living things
o Eukaryotic cells (i.e. human cells) are classified by
three different things:
1. Cell membrane
o Phospholipid bilayer surrounding the
structure
2. Nucleus
o Phospholipid bilayer surrounding the
structure
3. Cytoplasm
CELL BIOLOGY: Note #1.
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II) INTERBASE
Figure 2. Overview of interphase.
Consists of:
o G1 phase
o G1/S checkpoint
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o S phase
o G2 phase
(A) G1 PHASE
Also called GAP 1
First phase in the cell cycle
Duration varies for certain types of cells = months or
years in G1 phase depending on the cell
G1 prepares the cell for replication and produce an
identical cell
o Cell that houses the same amount of genetic material
(i.e. chromosomes)
Recall:
Diploid (2n)
o Cells containing a total of two sets of
chromosomes
o In humans, cells have a total of 46 chromosomes
 23 paternal chromosomes
 23 maternal chromosomes
o n = number of chromosomes
Figure 3. Replication of diploid cells.
(1) Functions
Make more organelles
o Increase number of organelles (e.g. ribosomes,
mitochondria)
o Why? Because you need organelles for two cells
Synthesize proteins and enzymes
o To aid in DNA replication
Repair thymine dimers
o There are different enzymes that can scan the DNA
for thymine dimers
(2) Types of Cells
Most of our cells stay in G1 phase
(i) Labile/Proliferative Cells
Cells that are constantly going through the cell cycle
Consist of:
o Epithelial cells of the skin, GIT and urinary tract
o Hematopoietic stem scells in the red bone marrow
 We have to be constantly making RBC, WBC and
platelets
(ii) Stable Cells
Cells that do NOT go through constant replication
Only replicate when there is a strong stimulus (e.g.
growth factors)
Consist of:
o Hepatocytes (liver)
 Can regenerate even though 40% of the liver is
resected
 Through release of growth factors
o Epithelium of the kidney tubules
o Alveolar cells of the lungs
(iii) Permanent Cells
Amitotic cells = cells that do not undergo replication
Consist of:
o Neurons
o Skeletal muscles
o Cardiac muscles
Thymine dimer
o DNA damage caused by exposure to ultraviolet
light [Rumora et al, 2008]
o Considered to be one of the more ‘bulky and
destabilizing’ lesions for several reasons [Rumora et al,
2008]
 Involves nucleotides locked in a rigid nonstandard shape
 Causes anomalous migration in gels and it
facilitates cyclization by bending DNA
 Blocks replicative DNA and RNA polymerases
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CELL BIOLOGY: Note #1.
Cell Cycle: Interphase & Mitosis
(B) S PHASE
Also called the synthetic phase
(1) Function
DNA replication
o Takes genetic material and open it up → forming a
replication bubble → making a new duplicate strand
from the single strand in the replication bubble
o Semi-conservative model
As the cell progresses through G1, it can either delay G1,
enter a quiescent state (G0), or proceed past the
restriction point [Alberts et al, 2007]
o DNA damage is the main indication for a cell to
“restrict” and not enter the cell cycle [Alberts et al, 2007]
Figure 4. DNA replication showing replication bubble (blue).
Semi-conservative replication model
o Two original DNA strands separate during
replication; each strand serves as a template for a
new DNA strand, which means that each newly
synthesized double helix is a combination of one
original and one new strand [Pray, 2008]
(C) G2 PHASE
Cell in this phase has 92 chromosomes (4n) with more
organelles
o However, cell did NOT have enough cytoplasm
Duration is about 2 hours
(1) Function
Cell growth
o By increasing the cytoplasm and different
components needed to make it bigger and equal for
replication
Table 1. Summary of interphase.
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Interphase
Function
G1 Phase
Make more
organelles
Synthesize
proteins and
enzymes
Repair thymine
dimers
Varies
according to
different cells
S Phase
DNA
replication
6 hours
G2 Phase
Cell growth
(increase
cytoplasm)
2 hours
Figure 5. Different DNA replication models [Biology LibreTexts] .
o DNA replication is maintained by DNA polymerase I
and III
 Can replicate DNA quickly and faithfully
o Replicates from 2n to 4n
 From 46 chromosomes to 92 chromosomes
o Constant in duration (~6 hours)
(2) G1/S Checkpoint
Makes sure that the replication has no issues; there is
enough proteins and organelles
Cell Cycle: Interphase & Mitosis
Duration
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III) MITOSIS
Also called the M phase
Duration: 1 hour
Consists of four parts:
o Prophase
o Metaphase
o Anaphase
o Telophase
 Cytokinesis
Figure 6. Overview of mitosis.
Mnemonic: PMAT
Prophase
Metaphase
Anaphase
Telophase
(A) PROPHASE
First phase of mitosis
(1) Functions
Condensation of chromatin
o Since the nucleus has a lot of loose DNA
(euchromatin), chromatin should be condensed in
order to separate the chromosomes
 Chromatin = DNA + histone proteins
Dissolution of the nuclear envelope
o The nuclear envelope needs to be dissolved to
separate the chromosomes into the opposite ends
o Special types of cyclin dependent kinases (CDK) that
phosphorylate different proteins of the nuclear
envelope
 Examples of proteins in the nuclear envelope:
lamins, H3A (histone protein)
o Phosphorylation → activates proteases → break up
the nuclear envelope
Formation of the microtubule organization center
(MTOC)
o Centrioles are markers of MTOC formation [Brinkley, 1985]
 Can gather during differentiation to become
MTOCs
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Figure 7. Prophase showing dissolved nuclear envelope,
condensed chromosome and MTOCs.
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CELL BIOLOGY: Note #1.
Cell Cycle: Interphase & Mitosis
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(B) METAPHASE
(1) Function
Prepares the chromosomes for separation
o MTOCs move towards the opposite poles of the cell
and connect to chromosomes via the polar
microtubules
Chromosomes are lined up perfectly in the middle
(metaphase plate)
(i) Chromosome
(C) ANAPHASE
(1) Function
Separation of sister chromatids
o Sister chromatids split away through splitting of the
cohesin and are transported to the opposite poles
 Cohesin: protein that glues the sister chromatids
together
o Motor proteins can “walk” the chromatids along the
microtubules
 Dynein: (-) end-directed protein
 Kinesin: (+)-end directed protein
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Figure 8. Different parts of the chromosome.
Made up of chromatin
Parts of the chromosome:
o Short arm (top)
o Long arm (bottom)
o Telomeres
 Found at the ends of the chromosomes
o Centromere
 Found at the center of the chromosomes
 Determine the number of chromosomes
o Sister chromatids
 Individual components of the chromosomes
o Kinetochore
 “Hook”-like structure where polar microtubules
connect to the chromosome
Figure 10. Anaphase showing the splitting of sister chromatids
and are transported to the opposite ends by motor proteins
(green).
Mnemonics:
Metaphase = middle = metaphase plate
Anaphase = away
Figure 9. Metaphase showing a perfectly lined up
chromosomes connected by polar microtubules.
Cell Cycle: Interphase & Mitosis
CELL BIOLOGY: Note #1.
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(D) TELOPHASE
Goal: Equal distribution of chromatin, cytoplasm, and
organelles into two cells
(1) Functions
Formation of the cleavage furrow
o Actin and myosin
 Contractile proteins
 Start contracting the cells producing a constriction
ring called cleavage furrow
Reformation of the nuclear envelope
o Recall that during the prophase, the nuclear envelope
dissolved
Distribution of chromatin and organelles
o Diploid (2n = 46) chromosomes are distributed in
each cell
 Since a nuclear envelope is reformed, chromatin
starts becoming loose
o Equal amount of organelles (e.g. ribosomes,
mitochondria, etc) is distributed
Cytokinesis
o Equal separation of cytoplasm
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Figure 11. Telophase showing equal distribution of chromatin,
cytoplasm, and organelles into two cells.
Table 2. Summary of the M phase.
M Phase
Function
Prophase
Chromatin condenses
Nuclear envelope dissolves
MTOC forms
Metaphase
Chromosomes line up perfectly in
the middle (metaphase plate)
Anaphase
Sister chromatids separate into the
opposite poles
Telophase
Cleavage furrow forms
Nuclear envelope reforms
Chromatin and organelles are
evenly distributed
Cytokinesis
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CELL BIOLOGY: Note #1.
Cell Cycle: Interphase & Mitosis
IV) MITOSIS MODELS
The following images are taken from the Ninja Nerd
lecture video:
Figure 12. The cell cycle represented in models.
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Figure 17. Telomerase showing the formation of the cleavage
furrow and cytokinesis.
V) WRAPPING UP
(A) FATES OF CELLS AFTER THE CELL CYCLE
Figure 13. Interphase showing a replicated loose chromatin.
Proliferative cells can go through the cell cycle again by
entering G1 phase
Some cells do not go immediately into the cell cycle and
go into the quiescent phase (G0 phase), where cells
remain dormant
o Stable cells go into the quiescent phase and only go
into the cell cycle after a strong stimuli
o Permanent cells do not go again into the cell cycle
and stay in the G0 phase
(B) TELOMERES AND CELL SENESCENCE
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Telomeres
o Located at the ends of chromosomes
Figure 14. Prophase showing a loose chromatin, mitochondrial
tubular organization center and dissolution of nuclear envelope.
Aging causes shortening of telomeres
o Cell senescence
 Cells are irreversibly out of the cell cycle
Figure 18. Aging causes shortening of telomeres.
(C) CELL CYCLE CHECKPOINTS
Figure 15. Metaphase showing the mitotic spindles on the
opposite sides, polar microtubules connecting to the
chromosomes, and the metaphase plate.
G1/S Checkpoint
o Makes sure there are enough organelles and proteins
for DNA replication
G2/M Checkpoint
o Makes sure there are no mistakes in DNA replication
o ATM genes
 Genes that produce proteins which can read the
DNA and check for errors
M Checkpoint
o Checkpoint after metaphase and before anaphase
o Makes sure that the chromosomes are aligned
perfectly in the metaphase plate
o Done by APC proteins, securins
Figure 16. Anaphase showing the separation of sister
chromatids into the opposite ends.
Cell Cycle: Interphase & Mitosis
CELL BIOLOGY: Note #1.
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VI) SUPPLEMENTARY IMAGES
Figure 19. (A) The cell cycle; (B) Length of cell-cycle phases in cultured cells; (C) Time scale of cell-cycle phases [Pollard et al, 2017].
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Figure 20. Cell cycle model [Eisco Labs].
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CELL BIOLOGY: Note #1.
Cell Cycle: Interphase & Mitosis
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VII) APPENDIX
Table 3. Summary of the cell cycle.
MITOSIS
INTERPHASE
Phase
G1 Phase
Make more organelles
Synthesize proteins and enzymes
Repair thymine dimers
Function
Remarks
Duration varies according to
different cells (labile, stable or
permanent)
S Phase
DNA replication
Duration: 6 hours
G2 Phase
Cell growth (increase cytoplasm)
Duration: 2 hours
Prophase
Chromatin condenses
Nuclear envelope dissolves
MTOC forms
Metaphase
Chromosomes line up perfectly in the middle (metaphase plate)
Chromosomes are connected to the MTOC via the polar
microtubules
Metaphase = middle =
metaphase plate
Anaphase
Sister chromatids separate into the opposite poles
Anaphase = away
Telophase
Cleavage furrow forms
Nuclear envelope reforms
Chromatin and organelles are evenly distributed
Cytokinesis
VIII) REVIEW QUESTIONS
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IX) REFERENCES
Which phase does the cell makes more
mitochondria?
a. G1
b. S
c. G2
d. G1 checkpoint
Which of the following statements is TRUE?
a. The equal distribution of cytoplasm happens during
anaphase.
b. MTOC is composed of centrioles and centrosomes.
c. Stable cells go on continuous cell cycle.
d. Chromosomes contain a long arm usually on the top
and a short arm on the bottom.
● Rumora, A., Kolodziejczak, K., Wagner, A., & Núñez, A. (2008).
Thymine Dimer-Induced Structural Changes to the DNA Duplex
Examined with Reactive Probes. Biochemistry, 13026-13035.
● Pray. (2008). Semi-Conservative DNA Replication: Meselson
and Stahl. Nature Education, 98.
● Alberts B, J. A. (2007). Molecular Biology of the Cell, 5th ed.
New York: Garland Science.
● Brinkley, B. (1985). Microtubule Organizing Centers. Annual
Review of Cell Biology, 145-172.
● Pollard, T., Earnshaw, W., Lippincott-Schwartz, J., & Johnson,
G. (2017). Cell Biology, 3rd ed. Philadelphia: Elsevier.
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Which of the following cells undergo replication
when a strong stimulus is detected?
a. Hematopoietic cells
b. Epithelium of the GIT
c. Epithelium of the skin
d. Epithelium of kidney tubules
How many chromosomes does the G2 phase has?
a. 23
b. 46
c. 92
d. 184
Which of the following statements is FALSE?
a. Telomeres at the ends of the chromosomes shorten
due to aging.
b. The permanent cells undergo indefinite stay in the
G0 phase.
c. The M checkpoint makes sure that the chromosomes
are equally distributed.
d. During the anaphase, the cohesin splits away and is
transported to the opposite side.
CHECK YOUR ANSWERS
Cell Cycle: Interphase & Mitosis
CELL BIOLOGY: Note #1.
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