Locating and isolating a gene, FISH, GISH, Chromosome walking and jumping, te...
B.Sc. Microbiology/Biotech II Cell biology and Genetics Unit 2 cell cycle
1. Cell biology and genetics Unit 2
Cell cycle and Cancer
Rai University,
Ahmedabad
2. 2
Cell Division
All cells are derived from pre-
existing cells
New cells are produced for growth
and to replace damaged or old cells
Differs in prokaryotes (bacteria) and
eukaryotes (protists, fungi, plants, &
animals)
3. 3
Keeping Cells Identical
The instructions for
making cell parts are
encoded in the DNA, so
each new cell must get a
complete set of the DNA
molecules
4. 4
DNA Replication
DNA must be copied or
replicated before cell
division
Each new cell will then
have an identical copy
of the DNA
Original DNA
strand
Two new,
identical DNA
strands
1
6. 6
Prokaryotic Chromosome
The DNA of
prokaryotes
(bacteria) is one,
circular chromosome
attached to the
inside of the cell
membrane
3
7. 7
Eukaryotic Chromosomes
All eukaryotic cells store genetic information
in chromosomes
Most eukaryotes have between 10 and 50
chromosomes in their body cells
Human body cells have 46 chromosomes or 23
identical pairs
8. 8
Compacting DNA into Chromosomes
DNA is tightly
coiled around
proteins called
histones
4
9. 9
Chromosomes in Dividing Cells
Duplicated
chromosomes are
called chromatids &
are held together by
the centromere
Called Sister Chromatids
5
10. 10
Karyotype
A picture of the
chromosomes from a
human cell arranged in
pairs by size
First 22 pairs are called
autosomes
Last pair are the sex
chromosomes
XX female or XY male
12. 12
Types of Cell Reproduction
Asexual reproduction involves a single cell dividing to
make 2 new, identical daughter cells
Mitosis & binary fission are examples of asexual
reproduction
Sexual reproduction involves two cells (egg & sperm)
joining to make a new cell (zygote) that is NOT
identical to the original cells
Meiosis is an example
13. 13
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
Parent cell
2 identical daughter cells
Chromosome
doubles
Cell splits
6
15. 15
Five Phases of the Cell Cycle
G1 - primary growth phase
S – synthesis; DNA replicated
G2 - secondary growth phase
collectively these 3 stages are called
interphase
M - mitosis
C - cytokinesis
16. 16
Interphase - G1 Stage
1st growth stage after cell division
Cells mature by making more
cytoplasm & organelles
Cell carries on its normal
metabolic activities
17. 7
Interphase – S Stage
Synthesis stage
DNA is copied or replicated
Two
identica
l copies
of DNA
Original
DNA
18. 18
Interphase – G2 Stage
2nd Growth Stage
Occurs after DNA has been copied
All cell structures needed for division are
made (e.g. centrioles)
Both organelles & proteins are synthesized
20. 20
Mitosis
Division of the nucleus
Also called karyokinesis
Only occurs in eukaryotes
Has four stages
Doesn’t occur in some cells
such as brain cells
8
21. 21
Early Prophase
Chromatin in nucleus condenses to form visible
chromosomes
Mitotic spindle forms from fibers in cytoskeleton
or centrioles (animal)
Chromosomes
22. 22
Late Prophase
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. 24
Spindle Fibers
The mitotic spindle form from the microtubules in
plants and centrioles in animal cells
Polar fibers extend from one pole of the cell to the
opposite pole
Kinetochore fibers extend from the pole to the
centromere of the chromosome to which they attach
Asters are short fibers radiating from centrioles
25. 25
Metaphase
Chromosomes, attached to the kinetochore
fibers, move to the center of the cell
Chromosomes are now lined up at the equator
Pole of the
Cell
Equator of Cell
9
29. 29
Telophase
Sister chromatids at opposite poles
Spindle disassembles
Nuclear envelope forms around each set of
sister chromatids
Nucleolus reappears
CYTOKINESIS occurs
Chromosomes reappear as chromatin
31. 31
Cytokinesis
Means division of the cytoplasm
Division of cell into two, identical halves
called daughter cells
In plant cells, cell plate forms at the equator
to divide cell
In animal cells, cleavage furrow forms to
split cell
32. 32
Daughter Cells of Mitosis
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)
33. 33
Eukaryotic Cell Division
Used for growth and repair
Produce two new cells
identical to the original cell
Cells are diploid (2n)
Chromosomes during Metaphase
of mitosis
Prophase Metaphase Anaphase Telophase Cytokinesis
12
35. 35
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
Cancer cells
13
37. 37
Facts About Meiosis
Preceded by interphase which includes
chromosome replication
Two meiotic divisions --- Meiosis I and Meiosis
II
Called Reduction- division
Original cell is diploid (2n)
Four daughter cells produced that are
monoploid (1n)
38. 38
Facts About Meiosis
Daughter cells contain half the number of
chromosomes as the original cell
Produces gametes (eggs & sperm)
Occurs in the testes in males
(Spermatogenesis)
Occurs in the ovaries in females (Oogenesis)
39. 39
Start with 46 double stranded chromosomes (2n)
After 1 division - 23 double stranded chromosomes
(n)
After 2nd division - 23 single stranded chromosomes
(n)
Occurs in our germ cells that produce gametes
More Meiosis Facts
40. 40
Why Do we Need Meiosis?
It is the fundamental basis of sexual
reproduction
Two haploid (1n) gametes are brought
together through fertilization to form a
diploid (2n) zygote
41. 41
Replication of Chromosomes
Replication is the process
of duplicating a
chromosome
Occurs prior to division
Replicated copies are
called sister chromatids
Held together at
centromere
Occurs in
Interphase
14
42. 42
A Replicated Chromosome
Homologs
(same genes, different alleles)
Sister
Chromatids
(same genes,
same alleles)
Gene X
Homologs separate in meiosis I and therefore
different alleles separate.
43. 43
Meiosis Forms Haploid Gametes
Meiosis must reduce the chromosome number by
half
Fertilization then restores the 2n number
from mom from dad child
meiosis reduces
genetic content
too
much!
The right
number!
44. 44
Meiosis: Two Part Cell Division
Homologs
separate
Sister
chromatids
separate
Diploid
Meiosis
I
Meiosis
II
Diploid
Haploid
45. 45
Meiosis I: Reduction Division
Nucleus Spindle
fibers
Nuclear
envelope
Early Prophase I
(Chromosome
number doubled)
Late
Prophase I
Metaphase I
Anaphase I Telophase I
(diploid)
47. • Prophase I
• It is the longest phase of meiosis. During prophase I, DNA
is exchanged between homologous chromosomes in a
process called homologous recombination. This often
results in chromosomal crossover. The new combinations
of DNA created during crossover are a significant source
of genetic variation, and may result in beneficial new
combinations of alleles. The paired and replicated
chromosomes are called bivalents or tetrads, which have
two chromosomes and four chromatics, with one
chromosome coming from each parent. The process of
pairing the homologous chromosomes is called synapses.
At this stage, non-sister chromatids may cross-over at
points called chiasmata
47
48. 48
Tetrads Form in Prophase I
Homologous chromosomes
(each with sister chromatids)
Join to form a TETRAD
Called Synapsis
53. 53
Meiosis II
Only one homolog of each
chromosome is present in
the cell.
Meiosis II produces gametes with
one copy of each chromosome and thus
one copy of each gene.
Sister chromatids carry
identical genetic
information.
Gene X
59. 59
Results of Meiosis
Gametes (egg & sperm) form
Four haploid cells with one copy
of each chromosome
One allele of each gene
Different combinations of alleles
for different genes along the
chromosome
61. 61
Mitosis Meiosis
Number of divisions 1
2
Number of daughter
cells
2 4
Genetically identical? Yes No
Chromosome # Same as parent Half of parent
Where Somatic cells Germ cells
When Throughout life At sexual maturity
Role Growth and repair Sexual reproduction
Comparison of Divisions
63. Cell cycle regulation
• The timing and rates of cell division in different parts of an
animal or plant are Crucial for normal growth,
development, and maintenance.
• The frequency of cell division varies with cell type.
• Some human cells divide frequently throughout life (skin
cells), others have the ability to divide, but keep it in
reserve (liver cells), and mature nerve and muscle cells do
not appear to divide at all after maturity.
64. A molecular control system drives the cell
cycle
• The cell cycle appears to be driven by specific chemical
signals in the cytoplasm.
• Fusion of an S phase cell and a G1 phase cell induces the
G1 nucleus to start S phase.
• Fusion of a cell in mitosis with one in interphase induces
the second cell to enter mitosis
65. • The distinct events of the cell cycle are directed by a
distinct cell cycle control system.
• These molecules trigger and coordinate key events in the
cell cycle.
• The control cycle has a built-in clock, but it is also
regulated by external adjustments and internal controls.
66. Checkpoints of cell cycle
• A checkpoint in the cell cycle is a critical control point where stop and
go signals regulate the cycle.
• Three major checkpoints are found in the G1, G2, and M phases.
67. G1 Checkpoint
• For many cells, the G1 checkpoint, the restriction point in mammalian
cells, is the most important.
• If the cell receives a go-ahead signal, it usually completes the cell cycle
and divides.
• If it does not receive a go-ahead signal, the cell exits the cycle and
switches to a nondividing state, the G0 phase.
• Most human cells are in this phase.
• Liver cells can be “called back” to the cell cycle by external cues
(growth factors), but highly specialized nerve and muscle cells never
divide.
68. • Rhythmic fluctuations in the abundance and activity of control
molecules pace the cell cycle.
• Some molecules are protein kinases that activate or deactivate
other proteins by phosphorylating them.
• The levels of these kinases are present in constant amounts, but
these kinases require a second protein, a cyclin, to become activated.
• Levels of cyclin proteins fluctuate cyclically.
• The complex of kinases and cyclin forms cyclindependent kinases
(Cdks).
69. G2 Checkpoint
• The G2 checkpoint prevents cells from entering
mitosis when DNA is damaged
• Providing an opportunity for repair and stopping
the proliferation of damaged cells.
• G2 checkpoint helps to maintain genomic
stability, it is an important focus in understanding
the molecular causes of cancer.
70. Spindle assembly checkpoints
• During mitosis and meiosis, the spindle assembly checkpoint acts to
maintain genome stability by delaying cell division until accurate
chromosome segregation can be guaranteed.
• Accuracy requires that chromosomes become correctly attached to
the microtubule spindle apparatus via their kinetochores.
• When not correctly attached to the spindle, kinetochores activate the
spindle assembly checkpoint network, which in turn blocks cell cycle
progression.
• Once all kinetochores become stably attached to the spindle, the
checkpoint is inactivated, which alleviates the cell cycle block and
thus allows chromosome segregation and cell division to proceed.
71. Apoptosis
• Apoptosis, or programmed cell death, is a
normal occurrence in which an orchestrated
sequence of events leads to the death of a cell.
• Death by apoptosis is a neat, orderly process
characterized by the overall shrinkage in volume
of the cell and its nucleus, the loss of adhesion
to neighboring cells, the formation of blebs at the
cell surface, the dissection of the chromatin into
small fragments, and the rapid engulfment of the
“corpse” by phagocytosis.
72. • Because it is a safe and orderly process,
apoptosis might be compared to the
controlled implosion of a building using
carefully placed explosives as compared
to simply blowing up the structure without
concern for what happens to the flying
debris.
73. • It has been estimated that 1010–1011 cells
in the human body die every day by
apoptosis.
• For example, apoptosis is involved in the
elimination of cells that have sustained
irreparable genomic damage.