2. Learning objectives
By the end of this session, students would be
able to:
• Briefly describe the cell cycle
• Explain cell reproduction
• Elaborate steps of DNA replication
• Enumerate the types and stage of cell division
3. Contents
• Cell cycle phases
• DNA replication
• Proof reading and mutation
• Mitosis & Meiosis (stages)
• Comparison of mitosis and
meiosis
• Role of telomeres
• Cell differentiation
5. Life Cycleof the Cell/Cellcycle
• The life cycle of a cell is the
period from cell reproduction
to the next cell reproduction
• Life cycle may be as little as
10 to 30 hours.
• Mitosis, however, lasts for
only about 30 minutes
• Interval between mitosis,
called
interphase
8. Cellsdivide at different rates
• The rate of cell division varies
with the need for those types
of cells
• Bone marrow cells divide every
10 hrs or less.
• Some cells are unlikely to
divide & remain in G0.
• Many nerve cells has cell
cycle of entire life.
9. CellReproduction Beginswith Replication of
DNA
• Cell reproduction is always done after replication
(duplication) of all DNA in the chromosomes.
• It is only after this replication has occurred that mitosis can take
place
• DNA begins to be duplicated 5 to 10 hours before mitosis,
and is completed in 4 to 8 hours
• After replication of the DNA, there is another period of 1 to 2
hours before mitosis begins abruptly.
12. Enzymesinvolved in DNAreplication
• Helicase: breaks hydrogen
bonds
• DNA primase: provides RNA
primer
• Principal enzymes: complex of
multiple enzymes called
DNA polymerase,
• DNA ligase, causes bonding of
successive DNA nucleotides to
one another
• Topoisomerase: break the
phosphodiester bond in DNA
strand to prevent DNA from
being overwound
13. DNAreplication
(leading strand)
DNA double helix starts unwinding in several points
(origin of replication)
↓ (Helicase)
Replication fork represent Y shape
↓
Primase puts primer (small chain of RNA) on the
template strand at origin of replication.
↓
DNA polymerase start putting nucleotide together
that are complementary to the parent DNA strand in
5’-3’ direction
↓
(the synthesis of new strand would be in antiparallel
manner)
↓
The new strand that is formed on 3’-5’ strand of
template DNA is a continuous strand & in 5’-3’ direction
& is known as leading strand
14. DNAreplication
(lagging strand)
Strand that is formed on other template is formed in
fragments (okazaki fragments) and called lagging strand
↓
DNA polymerase do elongation of strands
↓
Ligase join the fragments together
↓
DNA polymerase also do proof read & rectify
mismatched
bases
+
Exonuclease, removes the RNA primers from the
original strands, and the primers are replaced with
appropriate bases
+
Topoisomerase, can transiently break the phosphodiester
bond
in the backbone of the DNA strand to prevent the DNA in
front of the replication fork from being overwound
15.
16. DNARepair,DNA“Proofreading,” and
“Mutation.”
• Period of active repair and
“proofreading” of the DNA
strands during G2 phase
• DNA polymerases and DNA
ligases
do the poof reading
• Mutation: Because of repair
and proofreading, mistakes
are rarely made in the
transcription process,
• When a mistake is made, it is
called a mutation →abnormal
protein
17. Chromosomesand their replication
• 46 chromosomes arranged in 23
pairs.
• Genes in the two chromosomes of
each pair are almost identical to
each other (alleles).
• Histones keep the DNA in
condensed state
• For transcription, regulatory proteins
decondense the histone packaging of
the DNA and allow small segments
at a time to form RNA.
• After replication-chromosome
duplicates- remain attached to each
other through centromere
• These duplicated but still attached
chromosomes are called chromatids
18. What ismitosis?
• Somatic cell division
consisting of nuclear
division & cytoplasmic
division (cytokinesis)
• Single cell divides to produce
two identical daughter cells
• Chromosomes condense at
the start of mitosis.
• Human genome is represented
by two separate sets of
chromosomes, one functional
gene of each pair is almost
always available to the child,
despite mutations
21. Control of cell growth andcell
reproduction
• However ,3 suggested
ways:
1. Growth often is controlled by
growth factors(coming from
other tissue)
2. Most normal cells stop growing
when they have run out of space
for growth.
3. Cells grown in tissue culture often
stop growing when minute
amounts of their own secretions
are allowed to collect in the culture
• The mechanisms that maintain
proper numbers of the different
types of cells in the body are still
poorly understood
When cells have formed acomplete
single layer, they stop dividing
(density-dependent inhibition).
22. Cancer cells do not exhibit
anchorage dependence
or density-dependent
inhibition
23. TelomeresPrevent the Degradation of
Chromosomes
• A telomere is a region of repetitive
nucleotide sequences located at
each end of a chromosome
• Prevent the chromosome
from deterioration during cell
division
• Each time a cell divides, an average
person loses 30 to 200 base
pairs from
the ends of that cell’s telomeres.
• In human blood cells, the length of
telomeres ranges from 8000 base
pairs at birth to as low as 1500 in
older people.
• Oxidative stress, inflammation, aging
→ shortening of telomeres to a
critical length → chromosomes
become unstable
→ cells die)
24. Roleof telomerase
• Enzyme telomerase adds
bases to
the ends of the telomeres so
that
many more generations of cells
can be produced
• Telomerase activity is usually
low in
most cells of the body → after
many generation, descendent
cells
will inherit defective
chromosomes
→ become senescent
→cease dividing
• Stem cells of the bone marrow,
25. Roleof telomerase in diseasein cancers
• In cancer cells, telomerase
activity is abnormally activated
• So, that telomere length is
maintained → cells replicate
over and over again
uncontrollably
• Telomere shortening protects
us from cancer and other
proliferative diseases.
26. Regulation of CellSize
• Cell size is determined
almost entirely by the
amount of functioning DNA
in the nucleus.
• If replication of the DNA
does not occur, the cell
grows to a certain size
and thereafter remains at
that size.
27. Celldifferentiation
• Cell differentiation: Changes in
the
physical and functional properties of
cells as they proliferate in the
embryo
to form the different body
structures and organs
• It results not from loss of genes but
from selective repression of
different gene promoters
• It has been supposed that the
cellular
genome begins at a certain stage of
cell
differentiation to produce a
regulatory
28. Takehome messages
• Cell cycle: period from one cell reproduction to the next
cell reproduction (G1, S, G2,M phases)
• DNA replicates during S phase
• DNA polymerase reads 3’ → 5’, synthesize in 5’ → 3’ direction &
need 3’ end free for addition of bases.
• DNA polymerase & DNA ligase do proofreading of
replicated DNA during G2 phase.
• Mutation :mistake during replication
• Telomerase prevent shortening of telomeres
• Cell differentiate by tissue specific repression or activation of
genes.
