mitosis, meiosis (prophase, metaphase, anaphase and telophase and regulation of cell cycle

1. CELL CYCLE & ITS
REGULATION
ARTI YADAV
Dept. of Botany
Dayalbagh Educational Institute, Agra

2. Cell Cycle
 Term cell cycle was proposed
by Howard and Pelc.
 Cell cycle is the cyclic
representation of events of
cell division.
 Cell division occurs in
recurrent manner with a
freedom to quit only at one
point in G1 phase.
 Cell cycle is a progressive
events, no chance of
retrogression.

3.  Potu Rao and Johanssen performed fusion
experiment of cells in different stages of cell cycle
using sendai virus as a fusogen and observed that
cell cycle occurs in a progressive ordered manner
having arrival of phases in forward side and there is
no chance of reverse.
 The experiments were as follows:
1. S – Phase + G2 phase = heterokaryon
(Synkaryon shows DNA repair but no DNA
replication)
2. G1 phase + G2 phase = heterokaryon
(Synkaryon shows only DNA repair)

4. Stages of cell cycle
I. I Phase (Interphase)
1. G1 phase
2. S phase
3. G2 phase
II. M - Phase
1. Karyokinesis
A. Prophase
B. Metaphase
C. Anaphase
D. Telophase
2. Cytokinesis
A. Cell plate formation
B. Cell furrow formation

5. Why cell divide?
 Cell is the site of metabolic reaction and
continuous metabolism in the cell increases its
cytosolic volume, number of ER, Golgi,
Mitochondria, Chloroplast and micro bodies.
 As a result nucleo-cytoplasmic ratio disturbed
and to restore its proportional ratio a cell has
to divide.
Note:
There are some permanently or terminally
differentiated cells such as Neurons and bone
cells which do not divide.

6. Why neurons and bone cells
never divide?
 Gene responsible for cytosolic growth
are repressed in these cells hence their
cytoplasm remain illdeveloped with
reduced cell organelles.
 Further these cells are specialized for
some special functions and gene
governing these functions have
selective expression.
 In plants differetiated cells are not
found because of totipotency.

7. Duration of various stages
of cell cycle
 One turn of cell cycle
is usually completed
in 24 h, observed
through the culture of
embryogenic cells.
 But this time period is
never constant
because different
type cells of different
species takes
different time period
for completion of one
turn of cell cycle.

8.  Range of variation in this time period may be from hrs to
years or days to years.
 The time period for M - Phase is nearly constant for all cell
types but the variations in time periods are reported in the
length of G1 S and G2 phases.
 Although all these three phases shows variations in length
but the G1 phase shows maximum variation.
G1 > S > G2 > M (Prophase > Telophase >
Metaphase > Anaphase)
*Metaphase is highly dynamic phase due to
microtubule formation and deformation.

9. I – Phase v/s M – Phase
 Metabolically most
active phase but
cytologically resting
phase.
 G1 is metabolically
and biochemically
most active phase.
 G1 > S > G2
 Metabolically resting
phase but cytologically
most active phase.
 Karyokinesis is
cytologically most
active phase.
 Prophase > Telophase >
Metaphase > Anaphase
I – Phase M – Phase
Note:
Prophase and Telophase are cytologically more and almost equally active phase

10. G0 Phase
 Also called phase of cell differentiation.
 In this phase cell quit from cell cycle hence also
called phase of cell quiscence.
 Quiscence of cell can be reversible or irreversible.
 Reversible quiscence is found in plant cells where
differentiated cells can show dedifferentiation and
enter in cell cycle.
 Irreversible quiscence is reported in animal cell like
neurons and osteoclasts which are permanently
differentiated cells and never shows dedifferentiation.

11. G1 Phase (1st Growth phase)
 It is the 1st growth phase after cell division.
 It is the initial phase of cell cycle in which cell matures
by making more cytoplasm and organelles.
 It is most durable and highly variable in length.
 In this phase cell carries on its normal metabolic activities and
events in the G1 Phase are:
 Biosynthesis of dNTPs (dATP, dGTP. dCTP, dTTP).
 Biosynthesis of amino acids.
 Synthesis of cyclin proteins.
 Active gene expression.
 Synthesis of energy currency (ATP) and (GTP)
 RNA synthesis (Transcription)
I – Phase (Interphase)

12. S Phase
 S Phase is called
synthesis phase.
 Events of S Phase:
 DNA is copied or
replicated (DNA
doubling).
 Histone synthesis
 Centriole synthesis
(centromere)
duplication.
12
Two
identical
copies of
DNA
Original DNA

13. Animations during S - phase
What the cell looks like
Cell
What’s occurring

14. G2 Phase (2nd growth phase)
 Occurs after DNA has been copied.
 Both organelles and proteins are synthesized.
 Events of G2 Phase:
 Repair of DNA damages which have occurred during DNA
replication.
 Histone DNA packaging to form chromatin
 Repression of gene activity (transcription) begins
(completed up to Anaphase)

15. 15
Sketch of the Cell Cycle
Daughter
Cells
DNA Copied
Cells
Mature
Cells prepare for Division
Cell Divides into Identical cells

16. Cell division

17. M – Phase (Maturation Phase)
 Karykinesis is of two types:
1. Open karyokinesis (conventional
type karyokinesis) – nuclear
membrane disintegrates before
separation of chromosome
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase
2. Closed karyokinesis
(karyochorisis or dinomitosis) –
nuclear membrane remain intact
e.g. Yeast, Diatoms and Fungi
 Cytokinesis is of two
types:
1. Cell plate formation
(in plants)
2. Cell furrow
formation
(in animals)
Karyokinesis (Division of nucleus) Cytokinesis (Division of
cytoplasm)

18.  Karyokinesis:
1. Mitosis (somatic cells)
2. Meiosis (germ cells)

19. General account of Karyokinesis
Characteristics events:
 The structural maintenance chromosomal proteins (SMC) binds to
chromatin to allow the condensation of chromatin, hence the
reduction of size.
 The SMC proteins are non – histone proteins and they are also
called cohessions.
 The SMC mediated chromatin condensation is called aconemic for
plectonemic condensation which reduce the chances of paranemic
coiling.
 Paranemic coiling offers barrier for the separation of chromatids
and if it occurs, it may leads to annueploidy or structural aberration
in chromosome.
1. Prophase

20. Transition of cell from G2 phase to Prophase

21.  The chromatin condensation through acronemic coiling
continuous till anaphase.
 The condensation of chromatin reduces the
transcriptional activity of genes.
 Phosphorylation of nuclear lamins occurs, thus
disassembly of nuclear lamina. This phosphorylation is
done by cdk-cyclin complex.
 Disorganization of nuclear envelop.
 ER disorganizes to vesicles.
 Nucleolus disappears due to the dispersal of its
components.

22.  Chromosomes along with their respective centromere get aligned in the
equatorial plane of the cell.
 Microtubule growth occurs through polimerization of tubulins to form
spindle fibers.
 Kinetochore grows through polimerization of tubulins on centromeres and
DAM 1 ring of 32nm gets attached to kinetochores.
 Large number of spindle microtubules originates from centrosome in animal
cells (Astral spindles).
 The growth of these microtubule spindles occurs through polymerization at
+ (plus) end.
 In plants the spindle microtubule formation is anastral because no
centrosome and the cationic zone and in some cases the Y – tubulin acts as
nucleation centres for microtubule polymerization.
2. Metaphase

23.  With regard to microtubule cytoskeleton formation, the
metaphase stage is called most dynamic stage of cell
division.
 The microtubule grows blindly towards the equator of the
cell and where they find their respective kinetochores
through search and capture method.
 This mechanism of search and capture by microtubule
spindle is called metaphase congression.
 Origin of large number of microtubules in bipolar manner
ensures that all chromosome will be captured during
search and capture methods thus reduce the chances of
aneuploidy.

24. Types of metaphase microtubule
spindles
 It gets attached to their
respective kinetochore.
 Discontinuous
microtubules from both
pole forces kinetochores
towards each other
hence decides the
equatorial plane of the
cell (metaphase plate).
 It continuously grow and
their length is maintained
by microtubule
depolymerization.
 They do not find
kinetochores in search
and capture method hence
they continue to grow and
reaches upto opposite
poles.
Discontinuous Continuous

25. Note:
 Continuous microtubules are helpful because:
1. Motor proteins can deliver the cargo from one side to
another side of the cell using these microtubules as
road.
2. They pushes the poles opposite to each other thus the
cell elongates and the cell takes the shape of dividing
cells.
 The motor proteins of kinesin group gets loaded over
chromatids at many places using the chromatids as
cargo.
 At the end of metaphase the APC is activated which
acts as ubiquitin ligase enzyme (E3 enzyme).

26.  APC causes polyubiquitinization at N-terminal Lys residues of
target proteins (Seccurin is the 1st target here and 2nd target is
cyclins).
 APC forms isopeptide bond of ubiquitin’s COOH group with
epsilon NH2 group of Lys thus APC act as ubiquitin ligase.
 Ubiquitin is a low molecular weight protein which is a death
signal to target protein.
 As a result of seccurin digestion the separase become on . The
separase is a Cys rich protease which cleaves the cohession and
other cohession associated proteins.
 As a result of separase activity the onset of anaphase occurs.

27. 3. Anaphase
Least durable phase of cell division as a result
of cohession cleavage, sister chromatids gets
separated and then attached motor proteins
load on microtubules.
Due to sister chromatid separation and motor
protein loading the contraction force is
developed on centromere which causes
detachment of centromeres (doubling of
centromeres).
This doubling of centromere is the
characteristic feature of Anaphase.
Upon centromere division, the two centromere
start to repel each other in opposite direction
due to similar net positive charge.

28.  As a result of centromeric repulsion and oppositely
oriented force of continuous spindle fibres, the
discontinuous spindle fibres shows conformational
bending hence the dissociation of MAP (microtubule
associated proteins) from microtubules and
depolymerization of microtubules begins from the plus
end and inside the kinetochore.
 Beta tubulins of microtubules hydrolyses their bound
GTP to GDP during depolymerization.
 The motor proteins continue to move on microtubule
with chromosome cargo at a rate of 1µm/sec.

29. 4. Telophase
 It is also called reverse prophase
because following events occur which
are direct reversal of prophase:
 The continuous degradation of cohesins
which is started from anaphase, leads to
the loss of acronemic coiling
(decondensation of chromatids)
 Nuclear envelope reassembles to form
nucleus, the assembly of nuclear
envelope occurs through the
dephosphorylation of nuclear lamins.
 Nucleolus reorganised in NOR (
nucleolar organizer region) of SAT
chromosome.

30. 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

31. Cytokinesis
Cleavage furrow in
animal cell
Cell plate in plant
cells

32. 1. Mitosis
 It was first reported by
strassburger in onion root tips.
 Only occurs in eukaryotes.
 Division of the nucleus occurs,
one parent cell divides into two
daughter cells and both have
identical chromosome
composition hence are genetically
homogenous.
 The chromosome no. and
karyotype of the cell remains
constant.
 It has four stages
 Does not occurs in some cells
such as Brain cells.
*if copy error occurs , then daughter
cell may be not identical.

33. Four Mitotic Stages
 Prophase
 Metaphase
 Anaphase
 Telophase

34. Early Prophase
 Chromatin in nucleus condenses to form
visible chromosomes
 Mitotic spindle forms from fibers in
cytoskeleton or centrioles (animal)
Chromosomes
Nucleolus Cytoplasm
Nuclear Membrane

35. Late Prophase
 Nuclear membrane and 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

36. Late Prophase
Nucleus & Nucleolus have disintegrated
Chromosomes

37. 37
Spindle Fiber attached to Chromosome
Kinetochore Fiber
Chromosome

38. Review of Prophase
What the cell looks like

39. 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

40. 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

41. Review of Metaphase
What the cell looks like
What’s occurring

42. Anaphase
 Occurs rapidly
 Sister chromatids
are pulled apart
to opposite poles
of the cell by
kinetochore
fibers.

43. Anaphase Review
What the cell
looks like
What’s
occurring

44. Telophase
Sister chromatids at opposite poles
Spindle disassembles
Nuclear envelope forms around each
set of sister chromatids
Nucleolus reappears
Chromosomes reappear as chromatin

45. Comparison of Anaphase & Telophase

46. 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)
What is
the 2n or
diploid
number?
2

47.  In mitosis doubling of genetic material occurs
during S – phase while it reduce to half during
Anaphase.
 Since doubling and halving of the genetic material
occurs only once hence chromosome no. remains
constant.
 Although the two daughter cells formed through
mitosis are almost genetically identical, yet there
may be exceptional differences, originated through
copy errors during S – Phase.

48. Significance of Mitosis
 Used for growth and repair
 Produce two new cells identical to the original cell
 Cells are diploid (2n)
 Mitosis is the only way to increase the cell no. without any
change in genetic material.
 Somatic cells or vegetative cells divide through mitosis only.
 The rate of mitotic division in a cell is set according to the
cytoplasmic growth of the cell hence the mitosis can be slow
or fast depending upon the status of the cell.
 Mitosis always maintains a gap between two rounds of a cell
division which is essential for:
1. Repair of DNA damages and
2. Cytoplasmic growth of the cell

49.  Mitosis is most significant for immune cells and
embryonic cells because they shows proliferation
according to the need through mitosis.
 Mitosis is helpful in the replacement of dead cells
by new daughter cells.

50. Disadvantages of Mitosis
 Mitotic division can be made uncontrolled if loss of
function mutation occur in tumor suppressor gene
and gain of function mutation occur in proto-
oncogenes.
 Uncontrolled mitosis can lead to the tumor
formation.

51. 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

52. Facts About Meiosis
 It was reported by Farmer and Moore in anther of onion
flower bud.
 Two meiotic divisions occurs and parent cell divides two
times thus giving rise to four daughter cells ---
 Meiosis I and Meiosis II
 Original cell is diploid (2n)
 Daughter cells are monoploid (1n)
 Meiosis is the feature of germ cells and germ cells are
committed to divide two times through meiosis I and II.
2.Meiosis

53.  Produces gametes (eggs & sperm or pollen grains & ovule)
 Occurs in the anther (microsporogenesis)
 Occurs in the ovaries (megasporogenesis)
 Daughter cells contain half the number of chromosomes as
the original cell
 Doubling of genetic material occurs only once (in S – Phase
before meiosis I) while the halving of genetic material occurs
twice thus the daughter cells receives only half of the genetic
material but this genetic material is complete genome (haploid
set) of an organism.
Facts About Meiosis

54.  Meiosis I is called reductional division or heterotypic division
because the ploidy level of meiocyte is reduce to half during meiosis I.
 This reduction of ploidy in meiosis I is due to the separation of
homologous chromosome sets in Anaphase I .
 After meiosis I meiosis II is essential because it separates the sister
chromatids which have been duplicated during S – Phase.
 The duplication of centromere occurs in Anaphase II. Hence meiosis II
is identical to mitosis that’s why it is called meiotic mitosis or
homotypic division or equational division.
 The 4 daughter cells formed through meiosis are genetically different
from each other (genetically heterogenous) . It is due the crossing over
which occurs in pachytene stage of meiotic prophase I.
Facts About Meiosis

55. 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

56. Fertilization – “Putting it all
together”
1n =3
2n = 6
1n 2n
In plants In animals

57. 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

58. A Replicated Chromosome
Homologs
(same genes, different
alleles)
Sister
Chromatids
(same genes,
same alleles)
Gene A
Homologs separate in meiosis I and therefore different
alleles separate.

59. Meiosis Forms Haploid Gametes
 Meiosis must reduce the chromosome number by half
 Fertilization then restores the 2n number
From male parent from female parent
meiosis reduces
genetic content
too
much!
The right
number!
F1 plants

60. Meiosis: Two Part Cell Division
Homologs
separate
Sister
chromatids
separate
Diploid
Meiosis I Meiosis II
Diploid
Haploid

61. Meiosis
 Prophase I
 Leptotene
 Zygotene
 Pachytene
 Diplotene
 Dikinesis
 Metaphase I
 Anaphase I
 Telophase I
 Prophase II
 Metaphase II
 Anaphase II
 Telophase II
Meiosis I Meiosis IIInterkinesis

62. Meiosis I
 This phase of cell division is responsible for
bringing genetic heterogeneity and the reduction of
ploidy level.
 Only the cells with even ploidy level can enter in
meiosis I round.

63. 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)

64. Prophase I
Early prophase
Homologs pair.
Crossing over
occurs.
Late prophase
Chromosomes condense.
Spindle forms.
Nuclear envelope fragments.

65. Prophase I
 It is longest and highly variable phase of meiosis.
 Higher variability in the length of prophase I is due to the
prolonged diplotene stage in mammalian oocytes and sea urchin
oocytes where oocytes may remain arrested in diplotene stage for
many years (12 – 45 years) this is called diplotene arrest.
Leptotene:
 In this stage bivalent (dyad) homologous chromosomes shows
homologous pairing to form tetravalent.
 In this regard meiotic prophase I is different from meiotic
prophase II and mitotic prophase because prophase I has
tetravalent chromosome while prophase II and mitotic prophase
has bivalent chromosomes.

66. Tetrads Form in Prophase I
Homologous chromosomes
(each with sister chromatids)
Join to form a TETRAD

67. Zygotene:
 In this phase synapsis of homologous chromosome sets occurs at
many points due to the formation of synaptonomal complex.
 Generally two nearer non-sister chromatids of a tetravalent
participates in synapsis.
 Centromere interferes with syneptonemal complex formation in its
close vicinity due to stearic clash offered by its structure that’s why
the genes nearer to centromere usually do not synapse freely hence
no free crossing over.
 Further the formation of one syneptonemal complex also interferes
with the formation of another syneptonemal complex in its nearer
area. This is called Interference(I).
 Syneptonemal complexes are the future sites of crossing over but not
the guaranteed sites of crossing over.

68. Pachytene:
 This is the stage characterized by crossing-over
events.
 Crossing over generally occurs in areas of
syneptonemal complex. Such crossing over are
called expected crossing over.
 But the actual crossing over or observed crossing
over may be lesser or higher than the expected, but
there are very less chances of higher cross-overs.
 Higher than the expected crossing over is possible
through coincidence.

69. Crossing-Over
 Homologous
chromosomes in a
tetrad cross over
each other
 Pieces of
chromosomes or
genes are
exchanged
 Produces Genetic
recombination in
the offspring

70. 70
Crossing-over multiplies the already huge number
of different gamete types produced by independent
assortment
Crossing-Over

71. Diplotene:
 In this phase of cell division chaismata are formed due to
the migration of DNA strands from one DNA molecule
to another DNA molecule in reciprocal manner.
 This is called homologous recombination.
 These chaismata are called holiday junction in holiday
model of homologous recombination.
 Dikinesis:
 The terminalization of chaismata occurs in this phase.
 According to holiday model, the resolution of holiday
junction occurs during dikinesis.

72. Metaphase I
 Equatorial plane of metaphase I has tetravalent
chromosomes attached by bipolar microtubule
spindles.
Homologous pairs of
chromosomes align
along the equator of
the cell

73. Anaphase I
 Separation of homologous chromosome sets occurs thus
tetravalent becomes bivalent and division of centromere not
required.
 The segregation of Mendelian factors occurs in Anaphase I.
Homologs separate and move
to opposite poles.
Sister chromatids remain
attached at their centromeres.

74. Telophase I
 Each anaphase plate receiving bivalent chromosome enters in telophase I
but here telophase I is not the true reversal of Prophase I.
 Telophase I reverses the prophase I for the following events:
 Nucleolus reorganisation
 Chromatin decondensation
Nuclear envelopes reassemble.
Spindle disappears.
Cytokinesis divides cell into
two.

75. It is the short resting phase between meiosis I
and meiosis II.
Interkinesis

76. Meiosis II
 Meiosis II is divided in following 4 phases:
1. Prophase II
2. Metaphase II
3. Anaphase II
4. Telophase II
 All these phases have similar characteristic
events to that of Mitosis except telophase.
 In telophase II tetrad is formed while in
mitotic telophase dyad is formed.

77. 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 A

78. Meiosis II: Reducing Chromosome
Number
Prophase II Metaphase II
Anaphase II
Telophase II
4 Identical
haploid cells

79. Prophase II
Nuclear envelope
fragments.
Spindle forms.

80. Metaphase II
Chromosomes align
along equator of cell.

81. Anaphase II
Sister chromatids
separate and move to
opposite poles.
Equator
Pole

82. Telophase II
Nuclear envelope
assembles.
Chromosomes
decondense.
Spindle disappears.
Cytokinesis divides cell
into two.

83. Results of Meiosis
Gametes 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

84. Comparing Mitosis
and Meiosis

85. 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

86. Cell Cycle Regulation
 The whole course of cell cycle is tightly regulated
by the protein players:
 Cyclin proteins (Regulatory proteins for cell
cycles)
 Cyclin dependant kinases (cdk) (Catalytic
proteins of cell cycle)
 Structural Maintenance Chromosomal Proteins
(SMC) (Non-Histone proteins)
 Anaphase Promoting Complex (APC)

87. Need of cell cycle regulation
 Necessary to maintain the integrity of genome of the cell
because the DNA replication in S – phase of cell cycle
creates copy errors and these copy errors should be repaired
before the next round of replication.
 Cell division is an expensive process hence cell requires
sufficient time for active metabolism to generate energy
currency and to synthesize required amount of proteome.
 Proper cytoplasmic growth of the cell before cell division is
required because the halving of cytoplasm has to be done
during cell division.
 The primary aim of cell cycle regulation is to prevent the
onset of mutations.

88. Key regulators of cell cycle
 Timothy Hunt, Paul Nurse and
Leland Hartwell (Noble Prize,
2001) two types of key regulators of
cell cycle in mammalian cells:
1. Cyclin (key regulatory protein)
2. Cdk (cyclin dependant kinases;
catalytic protein)
 Beside these two key regulators,
other regulators also have
significant role in cell cycle
regulation such as:
1. Rb protein
2. P53 protein
Tumor Suppressor
Protein

89. Cyclin
 Regulatory proteins of cell cycle and shows
continuous rise and fall during the various stages of
cell cycle.
 Synthesis of cyclin proteins begins during G1 phase
and they increases their concentration till
Metaphase but in Anaphase they are degraded by
the activity of APC.
 The degradation of cyclin proteins at Anaphase
stage occurs through the APC mediated
polyubiquitinization.

90. Functions of cyclin proteins
1. Cyclin proteins binds to inactive cdk enzyme and
causes activation of these enzymes.
2. Cdc is the active stage of cdk which causes selective
phosphorylation of target proteins in following
manner.
3. Cdc causes transfer of ATP driven phosphate on the
serine or threonine residues of the target protein,
hence these cdc are also called Ser/Thr kinases.
4. Phosphorylation causes covalent modulation of target
proteins.

95.  Following are the target proteins for cdc in the cell:
 E2f
 Histones
 Nuclear Lamins
 APC

96. Types of regulatory cyclins
1. Cyclin A – G2 cyclin
2. Cyclin B – Mitotic cyclin
3. Cyclin D – G1 cyclin
4. Cyclin E – Late G1 S cyclin
D E A B is the working sequence of cyclins.

97. Cyclin D (G1 cyclin)
 Its higher concentration is reported in G1 phase
hence it is called G1 cyclin.
 It binds with cdk2 enzyme and causes the
activation of cdk2 by means of forming cdc2.
 It helps in the progression of cell cycle across G1
phase.

98. Cyclin E (Late G1 – S cyclin)
 Its concentration begins to increase at the end of G1
phase and it reaches at the peak during S – phase.
 It binds with cdk4 thus forming active cdc4.
 It allow the cell to progress from G1 phase to S –
phase.
 It causes activation of replicons in DNA thus the
replicon becomes Ori site (origin of replication or
replication bubble).

99. Cyclin A (G2 phase)
 It increases its peak concentration at G2 phase and
allow the cell cycle progression from G2 to M
phase.
 It activates cdk1 to cdc1.

100. Cyclin B (Mitotic Cyclin)
 It increases at peak during metaphase stage of cell cycle and it
causes the progression of cell from metaphase to anaphase by
means of activating cdk20 thus forming cdc20.
 Cdc 20 binds with APC thus APC gets activated.
 Almost all cyclin proteins begins to synthesize in G1 phase
and they reaches their peak in different stages of cell cycle
while their concentration suddenly falls down during
anaphase.
 Cyclin E is reported to be present in nearly constant
concentration from their synthesis till anaphase. It means
cyclin E is the long lived cyclin protein.
 Researcher believe that it is due to the proper folding of N
terminal of cyclin E, thus not freely accesible to E3 enzyme,
till the half life is achieved.

101.  In A. thaliana, 50 genes encode cyclin-related proteins
 Where 32 cyclins have putative functions in cell-cycle
regulation:
 10 A-type (encoded by10 genes),
 11B-type (11 genes encodes it),
 10 D-type (encoded by10 genes), and
 1 H-type cyclins (encoded by single gene)

102. Graph of cyclin conc. v/s cell cycle phases

103. Cyclin dependent kinases (CdKs)
 These are Ser-Thr kinases which acts as catalytic proteins for
cell cycle.
 They remain inactive when unbound to cyclins. They are
activated upon cyclin binding hence there is no need of
regulation of CdK concentration by rise and fall method
because it is regulated in this manner.
 The CdK concentration remains nearly constant throughout
the cell cycle, but they remain inactive and activated only
upon cyclin binding.
 Thus cyclin is most important key regulator of cell cycle and
it regulates the activity of CdK.
 There are many different isoforms (isozymes or isoenzymes)
in CdK group which acts in different stages of cell cycle with
different kinetic parameters (Vmax and Km)

104. Different types of CdK
1. CdK1
2. CdK2
3. CdK 4
4. CdK 20
 G2 to M
 G1 to S
 G1 to S
 Metaphase to
anaphase

105. Rb Protein (Retinoblastoma protein)
 It is the tumor supressor protein, Ist discovered in
patient suffering from retinoblastoma, hence the
name Rb given.
 Retinoblastoma is a tumor of eye retina which occurs
due to mutation in Rb gene, thus forming mutant Rb
proteins.
 Rb is a tumor supressor gene in mammals and its
product called Rb protein prevents the cell to migrate
from G1 to S phase.
 Thus Rb protein acts as the break for the cell cycle
progression from G1 phase.

106. Working of Rb protein in normal cell
Rb
Active TF
Allows expression of genes coding
for replication initiation protein
Inactive TF

107. P 53 Protein (Guardian of genome)
 A protein of 53 kd coded by a gene called P 53
gene or TP 53 gene.
 Acts to maintain the genome integrity of organism
because it pushes a cell towards apoptosis at any
stage of cell cycle when a cell has DNA damage.
 In this regaed P53 is called as the guardian of the
genome and the main tumor supressor gene.

108. Role of P 53 in Healthy and Tumor cells
In healthy cells
p53 get poly-
ubiquitinized and
degraded by 26s
proteasome

109. Regulation check points of cell cycle
 Although the cell cycle is
regulated at all stages of its
progression but some steps of
cell cycle are tightly regulated,
thus tightly regulated
checkpoints are called check
points or transition points.
 Following are the 3 main
transition checkpoints in cell
cycle:
1. G 1 to S
2. G 2 to M
3. Metaphase to anaphase

111. G1 to S transition checkpoint
 Known as START in Yeast and restriction point in
mammals.
 For transition cell requires active E2 F
 E2 F is activated by cyclin D – cdk complex
 In the absence of cyclin – D cell quit from cell
division and enters in G0 phase
 If active E2 F is avalable in the cell, it enters in
nucleus and activate genes for replication initiation.

112. How the cell passes from G1 to S phase

113. G1 to S phase transition in plant cell
Role of
phytohormone
and other
environmental
factors in cell
cycle regulation
• CYCD3 genes are the
key targets of cytokinin
that promote cell
division.
• CYCD3 expression
was also upregulated
by brassinosteroid

114. G2 to M – Phase checkpoint
 To cross this check point phosphorylation of nuclear lamins
required
 Phosphorylated nuclear lamins disintegrates hence onset of M –
phase (prophase) occurs

115. DNA damage checkpoint pathways in mammals and plants
 (A) DNA damage checkpoint mechanism in mammals
 (B) DNA damage checkpoint mechanism in A. thaliana Orthologs of Chk1,
Chk2, and Cdc25 have not been identified in plants

116. Metaphase to Anaphase or Spindle
assembly checkpoints

117. Cell Cycle Control in Plant
Control of the mitotic cycle and
endocycle.
 (A) In the mitotic cell cycle, a high
level of CDK activity triggers entry
into M phase and inhibits S phase
entry by preventing pre-RC
formation. At the end of mitosis,
APC/C induces cyclin degradation and
thus lowers CDK activity, leading to
pre-RC formation on chromatin.
 (B) In endoreduplicating cells, CDK
activity is lowered by the action of
CCS52A1-APC/C and the CDK
inhibitors SIM/SMR and KRP. Low
CDK activity leads to the inhibition of
M phase entry and the activation of
rereplication.

118. An overview of cell cycle regulation