CELL CYCLE ,MITOSIS , MEIOSIS AND CELL REGULATION

1. CELL CYCLE AND
REGULATION

2. CONTENTS
• CELL CYLCE
• PHASES OF CELL CYCLE
• MITOSIS
• MEIOSIS
• CELL REGULATION

3. CELL CYCLE
• very important processes in all living organisms
• During the cell division, DNA replication and cell growth takes place
• “The sequence of events by which a cell duplicates its genome, synthesizes
the other constituents of the cell and eventually divides into two daughter
cells is termed as cell cycle”
• “Rudolf Virchow” suggested “omnis cellula e cellula” means every cell is
derived from pre- existing cells.
• The duration of the cell cycle varies greatly from one cell type to another cell

4. CELL CYCLE
• A single-celled yeast can divide every 90-120minutes
• While a mammalian liver cell divides on average less than once a
year
• Muscle cells, nerve cells, and RBC are the only cells in our body
which do not divide
• Before discussion about cell division first we should know the
following terms

5. Cell cycle
• CHROMATIN:
• DNA coiled around histone proteins
• CHROMATID:
• one half of a duplicated chromosome
• CHROMOSOME:
• are two chromatids together , made of condensed chromatin

6. CENTROMERE
• the constriction region that divide the chromosome into two
chromatids
• primary constriction of the condensed chromosome
• clearly visible with a light microscope
• made up of highly repetitive condensed AT rich, heterchromatic DNA
with non-histone proteins
• cannot bind with microtubules themselves
• it is the site for kinetochore assembly
• it ensures delivery of one copy of each chromosome to each daughter
at cell division

7. kinetochore
• Kinetochores are disc shaped protein complexes intimately
associated with centromere
• Kinetochore can only be seen using electron microscope
• It is the site of assembly and disassembly of microtubules
• Made of multiple proteins

8. kinetochore
• It has a trilaminar structure the inner layer is in close contact
with condensed centromeric heterochromatin microtubules are
attached to the outer layer
• Made up of specialized types of histones like CENP-A
• Attachment site for spindle microtubule
• Involved in the movement of chromosomes during mitosis and
meiosis

10. CELL DIVISION IN PROKARYOTES
•By binary fusion

12. CELL DIVISION IN EUKARYOTES
A typical eukaryotic cell
cycle is classified into two
phases
1. interphase
2. M phase

13. INTERPHASE
• It is a long, metabolically active phase between two
successive mitotic cell division, it has three sub
stages
• Approximately 95% of the cell cycle is spent in
interphase

14. G1 PHASE
• The period between the end of M phase and the start of DNA
replication
• Last for about 11 hours
• Cell is metabolically active and continuously grows
• Do not replicate its DNA
• Raw materials (enzymes,ATP) required for the S phase synthesized
• Increase in cell size

15. S PHASE
• Also called synthesis phase
• Period during which DNA replication takes place
• The amount of DNA per cell divides from 2C to 4C
• But the number of chromosome remains same i.e., 2N
• In animals, centriole also divides in cytoplasm but not in plants due to
the absence of centriole

16. G2 PHASE
• The gap period between the DNA replication and the
initiation of M phase
• The synthesis of proteins required for the synthesis of
spindle fibres takes place
• Cell growth continues
• ATP synthesis increases
• Synthesis of plasma membrane proteins takes place

17. G0 STAGE
•Also called “quiescent stage or inactive stage”
•Cells that do not divide and exit G phase and enter an inactive
stage called Go stage
•Cells at this stage remain metabolically active but do not
proliferate
•Cells are able to enter reversible or irreversible Go stage

18. Go stage
•Quiescent state represent a reversible resting stage, cells in this
stage remain metabolically active and do not proliferate unless
depending on the requirement
•Senescent cells are dysfunctional cells that have ceased
proliferation and are permanently withdraw from the cell cycle
•Terminally differentiated cells(muscle cells and nerve cell) are
those cells that in the course of acquiring specialized functions,
have irreversibly lost its ability to proliferate

19. M PHASE
• mitotic phase
• It is a short phase
• It includes two important processes that occur simultaneously they are
karyokinesis (division of the nucleus) and cytokinesis (division of the
cytoplasm) resulting in two daughter cells
• After M phase the cell may enter interphase to repeat the cell division
or Go phase to arrest the cell cycle

20. M PHASE
• Two transient cytoskeletol structures that mediate M phase
in animal cells.
• Mitotic spindle assembles first to separate the chromosome
• Contractile ring ( actin and myosin filaments) assembles to
divide the cell in two

22. MITOSIS
• It was first observed by strasburger in plant cells and Boveri and Flemming in animal
cells
• It is a type of cell division in which a parental cell produces two similar daughter
cells that resembles the parental cells.
• Also called equational cell division because there is no change in chromosome
number
• Occur in somatic cells of the body , so it is also called somatic cell division
• Mitosis occurs in two stages i.e 1.karyokinesis 2. Cytokinesis

23. KARYOKINESIS:
• It is the division of nuclear material, it
occurs in four stages as follows
1.PROPHASE:
• It is the longest phase
• Chromatin begins to condense and becomes
visible in light microscope as chromosomes
• Centrioles move towards the opposite poles
• Spindle apparatus begin to appear

24. PROMETAPHASE:
• Starts with the breakdown of the
nuclear membrane
• Chromosome can now attach to
spindle microtubules via their
kinetochores, and undergo active
movement
• Nucleolus disappear
• Chromosome are set free in the
cytoplasm

25. they are three classes of microtubules
in a mitotic spindle
1.kinetochore microtubule: which
attach to the kinetochore region of the
chromosome
2.polar microtubules: microtubules do
not interact with the chromosomes but
overlap with polar microtubules from
the opposite pole
3.unattached microtubules: which are
unattached and are free

26. METAPHASE:
• Spindle fibres are completely formed
• The chromosome become short and
thick with two distinct chromatids each
• All the chromosome move towards
the centre of the cell and arrange in the
equatorial plane to form metsphasic
plate
• Chromosomes are attached to spindle
fibres at their kinetochore region

27. ANAPHASE:
• The paired chromatids separate to
form two daughter chromosomes
• Daughter chromosomes are pulled
towards the pole
• Chromosome number changes
from 2N to 4N (due to the
separation of chromatids)

28. TELOPHASE:
The daughter chromosome reach the opposite poles
Nucleolus and nuclear membrane reappears
The spindle fibres disappear
CYTOKINESIS:
It is the division of protoplasm into two daughter cells after
karyokinesis
The contractile ring (actin and myosin filament) assembles to
divide the cell into two cells
In plant cells, cell wall formation begins in the centre and
grow outwards
In some organisms karyokinesis is not followed by
cytokinesis ,leads to the formation of syncytium (liquid
endosperm in coconut)
Membrane bound organelles are usully present in large
number and will be safely inherited , but other organelles like
golgi complex , ER break up into small fragments during
mitosis

30. SIGNIFICANCE OF MITOSIS:
• It maintains genetic stability with in the population
of cells derived from same parental cell
• It helps the growth and tissue repair
• It helps in the replacement of dead and worn out
cells
• It is a means of reproduction in lower animals
• Takes place in somatic cells
• There is no change in chromosome number so called
equational division

32. MEIOSIS
• The term meiosis was coined by Former and Moore
• Type of cell division in which the daughter cells receive only half of
the original set of chromosome of the parental cell so called
reductional division
• Reduction of chromosome number is done by one round of DNA
replication being followed by two rounds of chromosome segregation
• Occurs only in germinal cells

33. MEIOSIS
• At the end of meiosis four daughter cells are formed
• Each of the daughter cell has one half of the number of
chromosomes as the parent
• Male gamete (sperm) and female gamete (ovum) fertilizes to form
diploid zygote develops into a individual having diploid numbers of
chromosome, so meiosis helps in maintain the constant number of
chromosomes

34. • INTERPHASE 1:
• As we already know during interphase the duplication of DNA,
centrioles and synthesis of RNA and proteins take place
•
• MEIOSIS I:
• KARYOKINESIS:
• PROPHASE I:
it is the longest phase of meiosis and divided into 5 sub stages

35. LEPTOTENE
• The chromatin condenses to form chromosome and visible under light
microscope
• Each chromosome has two chromatids that are not distinctly visible
• Also called as bouquet stage because the chromosome ends are attached to
the inner nuclear envelop and helps in homologous chromosome pairing and
synapsis
• Centriole move towards outer pole
• Spindle apparatus begin to appear

36. ZYGOTENE
• Pairing of homologous chromosome takes place called synapsis. The
pair is called bivalent
• Synaptonemal complex is a protein complex that forms between
homologous chromosomes
• The chromosome continues to undergo condensation
• Centrioles moving towards opposite poles

37. PACHYTENE
• The chromosome become more short and thick
• Each bivalent shows four chromatids called tetrad
• In this stage the exchange of genetic material takes place between the
non sister chromatids of homologous chromosome this process is
called crossing over
• Results in genetic recombinations which is responsible for variations

38. DIPLOTENE:
The beginning of the diplotene is
recognized by the dissolution of
the synaptoneimal complex
And the chromosome separated
at each other except at the sites of
crossing over
X – shaped structures are called
chaismata

39. DIAKINESIS
• Terminalisation of chaismata
• Chromosome is fully condensed
• At the end nucleolus and nuclear envelop disappears

41. METAPHASE:
•Spindle fibres are completely formed
•The chromosome become short and
thick with two distinct chromatids each
•All the chromosome move towards the
centre of the cell and arrange in the
equatorial plane to form metsphasic
plate
Chromosomes are attached to spindle
fibres at their kinetochore region

42. ANAPHASE:
The homologous
chromosomes separate,
while sister chromatids
remain associated at their
centromeres

43. TELOPHASE:
• The homologous chromosome reach the
opposite poles
• Nucleolus and nuclear membrane reappears
• The spindle fibres disappear
CYTOKINESIS:
• It is the division of protoplasm into two
daughter cells after karyokinesis

44. INTERKINESIS
• The interphase after the first meiotic division is called
interkinesis
• Or the time gap between the meiosis I and meiosis II
• Generally it is short or may not occur at all
• No DNA replication occur during this stage

45. MEIOSIS II
• Similar to the normal mitosis
• There is no S phase
• The chromatids of each chromosome are no longer
identical because of recombination during prophase I of
meiosis I

46. SIGNIFICANCE OF MEIOSIS
• It helps to restore diploidy and maintain the constant number of
chromosomes for a species
• Meiosis produce new combination of chromosomes and genes
by crossing over
• Increases the genetic variations ,important for the process of
evolution
• Reduction of chromosome number so called reductional division

48.  MITOSIS  MEIOSIS
Take place in the somatic cells of the body Take place in the germ cells
Occurs in both sexually as well as asexually
reproducing organisms
Occurs only in sexual reproducing organisms
The cell divide only once There are two cell divisions the first and the
second meiotic division
Interphase occur prior to each division Interphase preceeds only in meiosis 1. It does not
occur prior in meiosis II
DNA replication takes place during interphase I DNA replication takes place during interphase I but
not interphase II
The duration of prophase is short usually of a few
hours
Prophase is comparatively longer and may take
days
Prophase is comparatively simple Prophase is complicated and divided into
leptotene,zygotene, pachytene, diplotene, and
diakinesis.
DIFFERENCE BETWEEN MITOSIS AND MEIOSIS:

49. The cell divides only once and the chromosome also divide
only once
There is no synapsis
There are two cell divisions but the chromosome divide only
once
Synapsis of homologous chromosome take place during
prophase
The two chromatids of a chromosome do not exchange
segments during prophase
Chromatids of two homologous chromosome exchange
segments during crossing over
The arms of the prophase chromatids are close to one another The arms of the chromatids are separated widely in prophase II
Chromosomes are already duplicated at the beginning of
prophase
When prophase I commences the chromosomes appear
single,(although DNA replication taken place in interphase I)
No bouguet stage is recorded Chromosome of animals and some plants show convergence
towards one side during early prophase I it is known as
bouquet stage
A synaptionemal complex is absent Synapsed homologous chromosome develop a synaptionemal
complex
Crossing over is absent Crossing over or exchange of similar segments between non
sister chromatids of homologous chromosomes usually take
place during pachytene stage

50. Chiasmata are absent Chiasmata or visible connections between homologous
chromosomes of bivalents are observed during
diplotene, diakinesis (prophase I) and metaphase I
In the metaphase plate all the centromeres line up in
same plate
In metaphase I the centromers are lined up in two planes
which are parallel to one other
The metaphase plate is made up of chromosome pairs The metaphase plate is made up of paired chromosome
pairs
Two chromatids of a chromosome are genetically
similar
The genetic constitution of the daughter cells is
identical to that of the parent cells
Two chromatids of chromosome are often genetically
different due to the crossing over
The genetic constitution of the daughter cells differs
from that of the parent cells. The chromosome of
daughter cells usually contain a mixture of maternal and
paternal genes
Division of the centromeres take place during anaphase There is no centromeric division during anaphase I
centromeres divide only during anaphase II
The chromosome seperates simulta-
neously during anaphase
Short chromosomes seperates early, separation of long
chromosome is delayed
Anaphase chromosome are single stranded Chromosomes are double stranded in anaphase I. but
single stranded in anaphase II
Similar chromosome move towards the opposite poles
in anaphase
Dissimilar chromosomes move towards the opposite
poles both in anaphase I and II

51. Spindle fibers disappear completely in telophase Spindle fibers do not disappear completely in
telophase I
nucleoli reappear at telophase nucleoli do not reappear at telophase
cytokinesis follows every mitosis. It produces two
new cells
cytokinesis often does not occur after the first or
reduction division. It is often simultaneously after
second division to result in four cells
The chromosome number remains constant at the
end of mitosis
the chromosome number is reduced from the
diploid to the haploid
it helps in multiplication of cells multiplication of cells is not involved
Take part in healing and repair Take part in the formation of gametes and
maintainance of chromosome number of the race

52. CELL CYCLE
REGULATION

53. CELL CYCLE CHECKPOINTS
• A checkpoint is one of several points in the
eukaryotic cell cycle at which the progression of a
cell to the next stage in the cycle can be halted until
conditions are favorable.

54. G 1 CHECKPOINT
• Damage to DNA
• external factors are evaluated at the G1 checkpoint
• Nutrient availability
• if conditions are inadequate, the cell will not be
allowed to continue to the S phase of interphase.

55. G 2 CHECKPOINT
• The G2 checkpoint ensures all of the chromosomes
have been replicated
• and that the replicated DNA is not damaged before
cell enters mitosis.

56. M CHECKPOINT
• The M checkpoint determines whether all the sister
chromatids are correctly attached to the spindle
microtubules before the cell enters the irreversible
anaphase stage.

59. Cell cycle control system
• the engine that drives the progression from one step of the
cell cycle to the next are a series of protein complexes
composed of two subunits
• 1.cyclins
• 2.cyclin dependent protein kinase
• Cyclin is a regulatory component ,CDK is catalytic and acts
as protein kinase

60. CYCLINS
• Named because they undergo a cycle of synthesis and degradation in
each cell cycle
• Four classses of cyclins
• 1.G1-cyclins
• 2.G1/S-cyclins
• 3.S-cyclins
• 4.M-cyclins

61. CYCLIN-DEPENDENT KINASE
• A family of functionally related protein kinases
• Add phosphate groups to target substrate
• Named so because their activity are regulated by cyclins
• The target protein for CDK phosphorylation are determined
by the associated cyclins because different cyclins are
present at different phases of the cycle

62. Cyclin dependent kinases
• CDK 4 and CDK6 only partner with D-type cyclins
• CDK 1 and CDK 2 bind to multiple cyclins (A,B,D,E)
• Cyclin E-CDK2 triggers S phase
• Cyclins D and CDK 4 and CDK 6 regulate events in early G1 phase
• Cyclin A-CDK 2 and cyclin A-CDK1 regulate the completion of S
phase and
• Cyclin B-CDK 1 is responsible for M phase

66. Regulation of activity of M-CDK complex
• 1.interaction of mitotic cyclin with CDK form complex
• 2.the CDK subunit can be phosphorylated at two regulatory
sites by Wee 1 at tyrosine-15 and by CAK at threonine -161
• When both residues are phosphorylated M-CDK is inactive
• Finally removal of the phosphate from tyrosine-15 by cdc25
phosphatase yeilds active M-CDK complex

68. INHIBITORS

69. DNA damage checkpoints
• ATM and ATR activated when any damaged or unreplicated DNA is
present
• ATM is activated principally by double stranded breaks and ATR by
single stranded or unreplicated break
• ATM and ATR the phosphorylate and activate the CHK2 and CHK1
• CHK1 and CHK2 phosphorylate and inhibit the Cdc25A and
Cdc25C(which are required for the activation of Cdk 2 and Cdk1)

71. role of p53
in G1 arrest
in response
to DNA
damage

72. • And they are several regulatory pathways
• 1.cell cycle regulation of Rb and E2F
• 2.the spindle assembly checkpoint
Unattached kinetochores lead to the assembly of a complex
of Mad/Bub protein in which Mad activated and prevent
APC activation by inhibiting Cdc20