The document provides an overview of the cell cycle, including mitosis and meiosis, cell regulation, apoptosis, and the characteristics of cancer cells. It discusses mechanisms controlling cell division, such as checkpoints and factors that influence cell proliferation, including growth factors and tumor suppressor genes like p53. Additionally, it outlines the genetic basis of cancer, including proto-oncogenes, oncogenes, and mutations that can lead to uncontrolled cell growth.

1. CELL
CYCLE
Muslima P. Liwalug
MIB 1

2. OUTLINE:
 Cell Cycle
 Cell Regulation
 Oncogenes
 Apoptosis
 Characteristics of Cancer

3. CELL CYCLE
Simple Cell Cycle
o Cell division in bacteria
takes places in 2
stages
• DNA is copied
• Cell splits (binary
fission)
o Heredity in bacteria
encoded in single
circle of DNA
Complex Cell Cycle
o Eukaryotic DNA is
contained in linear
chromosomes
• long DNA molecules
packaged w/ proteins
o Mitosis - Mechanism of
cell division occurring in
non-reproductive
(somatic) cells
o Meiosis - Mechanism of
cell division occurring in
reproductive (germ) cells

5. MITOSIS

6. A B
C D

7. MEIOSIS

9. PROPHASE 1
1. Leptotene
• Pairing. Homologous dyads (pairs of sister
chromatids)
• Thread-like chromatin with bead-like
chromomeres
• Plants- chrom drawn in 1 side of nucleus
(synizesis)
• Animals- drawn toward part of nuclear
membrane close to centriole
2. Zygotene
• The synaptinemal complex begins to form.
• DNA strands of nonsister chromatids begin
recombination.
3. Pachytene
• Synapsis is now complete.
• Recombination The steps in recombining
DNA continue to the end of pachytene.
• Crossing over involves chromatid breaks and
repairs
• Tetrad/bivalent formation occurs
4. Diplotene
• DNA recombination is complete.
• The synaptonemal complex begins to
break down.
• Coiled nature of chrom very apparent
• The chromatids begin to pull apart
( terminalization) revealing chiasmata.
5. Diakinesis
• Chrom assume unique configurations
due to repulsion of chromatid pairs
• This is followed by the chromosomes
recondensing in preparation for
metaphase I.
• Bivalents bec distributed evenly in
nucleus
• Nucleolus disintegrates and spindle
fibers form

12. MITOSIS MEIOSIS
PARENT CELL
(before chromosome replication)
Site of
crossing over
MEIOSIS I
PROPHASE I
Tetrad formed
by synapsis of
homologous
chromosomes
PROPHASE
Duplicated
chromosome
(two sister chromatids)
METAPHASE
Chromosome
replication
Chromosome
replication
2n = 4
ANAPHASE
TELOPHASE
Chromosomes
align at the
metaphase plate
Tetrads
align at the
metaphase plate
METAPHASE I
ANAPHASE I
TELOPHASE I
Sister chromatids
separate during
anaphase
Homologous
chromosomes
separate
during
anaphase I;
sister
chromatids
remain together
No further
chromosomal
replication; sister
chromatids
separate during
anaphase II
2n 2n
Daughter cells
of mitosis
Daughter cells of meiosis II
MEIOSIS II
Daughter
cells of
meiosis I
Haploid
n = 2
n n n n
MITOSIS VS. MEIOSIS

13. REGULATING
THE
CELL CYCLE

15. CELL CYCLE CHECK POINTS
o Control loops that
make initiation of one
event dependent on
the successful
completion of an
earlier event
o Prevent damage that
would ensue if cell
were to undergo
premature activity

16. CELL CYCLE CHECK POINTS
o checkpoint for division
ensures that the previous
mitosis is finished
o checkpoint for DNA integrity
ensures that all DNA is
replicated and that there is no
damage to it
o checkpoint for unreplicated
DNA
ensures that all DNA is
replicated and replicated only
once
G1 checkpoint
M checkpoint G2 checkpoint
Control
system

17. Growth factor
Figure 8.8B
Cell cycle
control
system
Plasma membrane
Receptor
protein
Signal
transduction
pathway
G1 checkpoint
Relay
proteins
THE BINDING OF GROWTH FACTORS TO SPECIFIC RECEPTORS
ON THE PLASMA MEMBRANE IS USUALLY NECESSARY FOR
CELL DIVISION

18. Control Mechanisms for cell division

19. Apoptosis – programmed
cell death
Schematic description of the controls in
cell proliferation

20. Controlling the Cell Cycle
• At critical points, further cell
progress depends on a central set
of switches regulated by cell
feedback.
– G1 – Cell growth assessed
– G2 DNA replication assessed
– M mitosis assessed
• Gene p53 plays a key role in G1
checkpoint of cell division.
– Gene’s product monitors
integrity of DNA, checking for
successful replication.
• If protein detects damaged
DNA, it halts cell division
and stimulates repair
enzymes.
– Nonfunctional p53
genes allow cancer cells
to repeatedly divide.

21. • Growth factors are proteins secreted by
cells that stimulate other cells to divide
After forming a single layer, cells
have stopped dividing.
Figure 8.8B
Providing an additional supply of
growth factors stimulates further
cell division.

22. Anchorage, cell density, and chemical growth factors affect cell division
In laboratory cultures, most normal cells divide only
when attached to a surface
– They are anchorage dependent
Cells anchor to dish surface and
divide.
When cells have formed a
complete single layer, they
stop dividing (density-
dependent inhibition).
If some cells are scraped away,
the remaining cells divide to
fill the dish with a single layer
and then stop (density-
dependent inhibition).
Cells continue dividing until they touch one
another (Contact Inhibition)
Growth factors are proteins secreted by cells
that stimulate other cells to divide
After forming a single layer, cells
have stopped dividing.
Providing an additional supply of
growth factors stimulates further
cell division.

23. FACTORS THAT CONTROL CELL DIVISION
1. cellular clock
•determines the number of times the cell divides
•dependent on cell type
•ex. Connective tissue cells- higher rate of division than adult cells
small intestine cells- divides during entire lifetime
2. Cellular inhibition
-Normal cells in culture grow in a monolayer
-When expanding monolayer encounters a barrier, it will grow around not over it
-When surface of culture dish is covered with cells growth stops
-Expression of orderly and limited cell growth
3. outside factors
-hormones- cells lining uterus dependent on human progesterone
Growth Factors
1. epidermal growth factor
whenever there is injury to epidermis
governed by contact inhibition
also present in saliva-animals lick wounds
2. Platelet-derived growth factor
- first identified to induce cell to divide in culture
4. intracellular factors
-Early 1970s- subs + non-dividing cell - cell divides
-Called it MPF- Maturation Promoting Factor
-1988 (Lohka and Maller)- isolated MPF from Xenopus laevis
-Induced cell to enter Mitosis (Called it M-Phase Promoting Factor)

24. Two Subunits of MPF
1. protein kinase-(p34 or cdc-2)
o phosphorylates tyrosine and threonine
o transfers phosphate groups from ATP to other proteins
that mediate cell cycle
2. cyclin (p45)
o -necessary for MPF to function
o -undergoes a cyclic of synthesis and degradation
o -control progression through cell cycle
o -defective cyclin results in uncontrolled cell division→
parathyroid tumor, breast cancer and leukemia

26. PREVENTING THE PROLIFERATION OF CANCER CELLS
 Tumor suppressor genes like p53
• Can arrest the cell cycle
• Can launch the apoptotic pathway, causing
the rogue cells to lyse
A mutation in the p53 gene can lead to cancer
 Immune cells (WBCs) such as NK cells can
attack and lyse tumor cells
• Some immune cells can signal the rogue
cells to launch the apoptotic pathways

27. CANCER
Genetic
basis of
cancer
Genetic disease at the cellular level
caused by an accumulation of mutations
over a lifetime

28. WHAT CAUSE TUMOR GROWTH
A. Proto-oncogenes
 proteins involved in growth and cell-cell interactions
B. Viruses
 contain ONCOGENES (gene that promotes cancer)
 Cancer genes which cause cell proliferation despite signal
saying ‘STOP’
 many cancers have no viral association
 Insert into our chromosomes and transforms
• Epstein-Barr Virus --> Burkitt’s Lymphoma
• Papillomaviruses --> cervical cancer
C. Tumor Suppressor Genes
• Normal gene - prevents cells from dividing
• when mutated - loss of function
• cells divides out of control
D. Loss of a cell´s ability to undergo apoptosis

29. o Tumors (neoplasms)
• new cells are being produced in greater numbers
than need
• organization of the tissue becomes disrupted
o Transformation
• Process of converting a normal cell into malignant
cell
• rate of cell proliferation has increased

30. CHARACTERISTICS OF CANCER
1. Clonal in origin – a hallmark of cancer cell is that
it divides to produce 2 daughter cells
2. Benign – non-invasive and precancerous genetic
change
3. Malignant – when cells becomes cancerous and
invasive to the neighboring cells
- becomes metastatic (they can migrate to other
parts of the body and cause secondary tumors)

31. CANCEROUS CELL
o Has large and multiple nuclei
o Irregular in shape
o Cells overlapping neighboring cells
o Loss of density – dependent or contact inhibition
o Loss of anchorage dependence

32. DISTINCTIVE APPEARANCE OF CANCER CELLS

33. CERTAIN VIRUSES CAN CAUSE CANCER BY
CARRYING VIRAL ONCOGENES INTO THE CELL
o 15% of all human cancers are associated with viruses
o Onco is incorporated into viral genome and this gene can
become a viral oncogene
Why does cancer occur when the gene is in viral genome?
1. Many copies of the virus made during viral replication may
lead to overexpression of src gene
2. The incorporation of the src gene next to viral regulatory
sequence may cause it to be overexpressed
3. The v-src gene may accumulate additional mutations that
convert it to an oncogene

34. A GAIN-OF-FUNCTION MUTATION THAT
PRODUCES AN ONCOGENE
1. The amount of the encoded protein is greatly
increased
2. A change occurs in the structure of the encoded
protein that causes it to be overly active
3. The encoded protein is expressed in a cell type
where it is not normally expressed

35. GENETIC CHANGES IN PROTO-ONCOGENES
CONVERT THEM TO ONCOGENES
1. Missense Mutation – changes of the structure of
Ras protein can cause it to become permanently
activated
2. Gene amplification – abnormal increase in the
copy number of a proto-oncogene
3. Chromosomal translocation – translocation
activates a proto-oncohgene
Philadelphia chromosome - shortened arm of
chromosome # 22