The document provides an overview of the cell cycle, including its key components and phases. It discusses cyclin-dependent kinases (Cdks) and cyclins, which activate during different phases to drive the cell cycle forward. It also describes important cell cycle regulators like the anaphase promoting complex (APC) and SCF complex that control progression by targeting proteins for degradation. The major phases of the cell cycle - interphase, mitosis, and cytokinesis - are summarized. Meiosis is also introduced as a type of cell division that reduces chromosome number. Molecular events underlying different cell cycle stages are highlighted.

1. CELL CYCLE
SUBMITTED BY
A.GOVARDHANI
RAM/18-106
Institute Of Biotechnology,
PJTSAU.

2. Introduction
• Definition
• Cdk’s And Cyclins
• APC
• SCF
• Interphase
• Mitosis
• Cytokinesis
• Meiosis
• Case Study

3. Can Be Defined As
• Entire sequence of events happening from
one end of one nuclear division to the
beginning of next.
• begins when two new cells are formed by the
division of a single parental cell and ends
when one of these cells divides again into two
cells.
• Cycle of duplications and division.(Molecular biology of cell-
Alberts)

4. Cdk’s And Cyclins
• Central components of the cell-
cycle control system are members
of a family of protein kinases
known as cyclin-dependent kinases
(Cdks).
• Cdk regulators are proteins known
as cyclins.
• Full activation of the cyclin-Cdk
complex then occurs when a
separate kinase, the Cdk-activating
kinase (CAK), phosphorylates an
amino acid near the entrance of
the Cdk active site

7. Four Classes Of Cyclins
• 1.G1/S cyclins bind to Cdk at the end of G1 and
commit the cell to DNA replication.
• 2.S-cyclins bind to Cdk during S-phase and are
required for the initiation of DNA replication.
• 3.M-cyclins promote the events of mitosis.
• 4. G1-cyclins, helps govern the activities of the
G1/S cyclins, which control progression
through Start in late G1.

9. APC
• key regulator of the metaphase-to-anaphase transition
is the anaphasepromoting complex, or cyclosome
(APC/C).
• APC/C catalyzes the ubiquitylation and destruction of
two major proteins.
• first is securin, protects the protein linkages that hold
sister chromatid pairs together in early mitosis.
• S- and M-cyclins are the second major targets of the
APCi/C.
• the APC/C remains active in G1,thereby providing a
stable period of Cdk inactivity. When G1/S-Cdks are
activated in late G, the APC/G is turned off, thereby
allowing cyclin accumulation to start the next cell cycle

11. SCF
• The cell-cycle control system also uses another ubiquitin
ligase called SCF(S- Phase kinase-associated protein 1 p19
[SKP1]/Cullin/F-box complex).
• Ubiquitylates certain CKI proteins in late G.
• helps control the activation of S-cdks and DNA
replication.
• SCF activity is constant during the cell cycle.
• Ubiquitylation by SCF is controlled instead by changes in
the phosphorylation state of its target proteins, as F-box
subunits recognize only specifically phosphorylated
proteins

12. Two Kinds of Cell Division
• MITOSIS
• MEIOSIS

13. Cell Cycle Consists Of Two Phases

14. Interphase
• Is generally known as DNA synthesis phase/Non-
diving phase.
• 3-Phases : G1, S and G2 Phases.
• G1 Phase : Pre DNA synthesis phase.
Most variable period of cell cycle.
• May even enter a specialized resting phase
known as G0 phase.

15. G1 Phase
Fully
extension
of
chromatin
material
Production
of t RNA,
m RNA,
r RNA.
Production
of
nucleolus
in
Interphase
nucleus
Production
of
proteins-
need in
various
stages of
mitosis
Enzymes-
DNA
Polymeras
e- helps in
DNA
synthesis
Tubulin
and other
proteins

16. G1 -Phase
Cdc6: Cell Division
Cycle 6,
Cdt1 : Chromatin
Licensing And DNA
Replication Factor
1,
MCM:
Minichromosome
Maintenance
Protein Complex

17. S-Phase

18. PCNA :
Proliferating Cell
Nuclear
Antigen.

19. G2 Phase
• Also called as resting phase, Second gap,
Growth phase, Preparation stages for the M-
phase.
• RNA, Proteins are produced which helps in
growth of the cell.
• Occupies 10-20% of the cell cycle

20. Centrosome Replication
•G1/ S-Cdk initiatesDNA replication in S-phase also stimulates centrosome duplication.
•M-Cdk activity initiates the spindle assemble.
• Amount of y-tubulin ring complexes in each centrosome increases greatly, increasing
the ability of the centrosomes to nucleate new microtubules, a processc alled
centrosome maturation

21. Mitosis
• The term Mitosis was coined by Flemming in
1882.
• Mitosis occurs in somatic cells like root
tip,stem tip and leaf bases etc. Hence it is also
known as somatic cell division.
• Daughter cells are similar to mother cell hence
this is also known as Homophytic or
equational division.

22. Stages Of Mitosis
• Prophase
• Prometaphase
• Metaphase
• Anaphase
Anaphase-a
Anaphase-b
• Telophase

23. Prophase
• Longest Mitotic phase.
• Duplicated chromosmes consists of two
chromatids.
• At the beginning of prophase chromosomes
appear as thin, filamentous uncoiled structure.
• Chromosomes becomes coiled, shortened and
more distinct.

25. Molecular Mechanism Of
Chromosome Condensation
• Sister chromatids are glued together by
multisubunit protein complexes called
Cohesins.
• condensation and resolution of sister
chromatids depends protein complex called
condensin.
• Condensin structure is related to that of the
cohesin complex that holds sister chromatids
together .

26. Smc- Structutal Maintenance of
Chromosomes
Scc – Sister Chromatid Cohesion

27. Prometaphase
• Breakdown of the nuclear envelope
• Chromosomes are being attached to spindle
microtubule via their kinetochore, and a spindle
structure is formed which has two distinct poles.
• The chromosomes are released into the
cytoplasm. But the growing microtubules form
the both centrosomes quickly hold the
chromosomes at their kinetochore and the
chromosomes are being arranged in the equator
in a line.

28. Chromoso
me in
active
motion

29. Molecular Events In Nuclear Membrane Breakdown
Nuclear laminas (A,B and C).The Phosphorylated lamina A and C dimers are
released into the cytoplasm.The Phosphorylated lamin B dimer remains
associated with the nuclear membrane with their isopropyl group.
MPF:
Maturation
Promotion
Factor

30. Microtubules

31. Bipolar Attachement

32. Attachment of Microtubule to
Kinetochore

34. Spindle Formation In Cells Without Centrosomes
• The microtubule nucleation and assembling property of
the chromosomes seem to be dependent upon the
guanine –nucleotide exchange factor(GEF) which is
bound to chromatin.
• This GEF stimulates a small GTPase in the cytosol called
Ran. Binds to GTP in place of GDP.
• The activated Ran-GTP complex releases microtubule-
stabilizing protein complex in the cytosol and stimulates
the local nucleation of microtubules around the
chromosomes.
• Astral microtubules are not produced.

35. In Plant Cell

36. Metaphase
•Chromosomes exhibit maximum coiling.
•Chromatids lie side by side .The Kinetochore regions of each chromatid
remain separate.
•Chromatids appear stationary because forces acting on them are equal in
magnitude and opposite in direction.

37. Molecular Events In Metaphase
• In vertebrate cells, the chromosomes at the metaphase
plate oscillate gently and awaiting the signal to
separate.
• The movement is seen to switch between two states : a
poleward state which is minus end directed pulling
movement, and an away from the pole state, which is a
plus end directed movement.
• The cells do not enter into anaphase until all
chromosomes are attached to both poles with the
spindle or may be said that unattached kinetochore
emits a signal that delays anaphase.

38. Anaphase
Anaphase consists of
Anaphase-A, Anaphase-B.

39. Chromosome movement was due to
depolarization of kinetochore microtubule

40. • Anaphase- A :
Kinetochore microtubules are shortened mainly by the loss of
tubulin from their kinetochore ends.
• Anaphase –B:
Polar microtubules slide past one another and elongate. Then
pulling forces are exerted by the cellular cortex on astral
microtubules.
Plus end directed motor proteins cross link the overlapping
antiparallel microtubules.
This motor protein is KRP and walks along a microtubule and
slides the microtubules past each other, thereby pushing
the spindle polewards.
In this process the energy is utilized from ATP hydrolysis.
Minus end directed motor protein cytosolic dynein binds to
the cell cortex and to those astral microtubules that point
away from the spindle and pulls the poles apart.
KRP:Kip Related
Protein

41. How Pulling Of Chromatid Takes Place?
Depolymerization: the
protofilaments of the
microtubule curl
outward and push
against the collar
structure, this will
move the kinetochore
toward the
microtubule minus
end at the spindle
pole.

42. Molecular Events Of Separation Of Chromatids
• Anaphase begins with a sudden disruption of
the cohesin between sister chromatids and
this process is initiated by a remarkable of
signaling events.
• A Protein Cdc-20 binds to APC (Anaphase
promoting complex).
• Activated APC degrade the M-Cyclin and
securin.

44. Telophase
Reassemble
Chromosme
Vesicles of ER become associated with the surface of the chromosome and
then fuse to reconstruct the nuclear envelope.
Nucleolus reappears and the RNA synthesis become active while the
chromatin becomes dispersed as in the interphase conformation.
The division of cytoplasm begins with the assembly of the contractile ring.

45. Formation Of Nuclear Membrane
Lamin A and C are imported through the reassembled nuclear pore
complex and reassembly is initiated on lamin B molecules.

46. Cytokinesis
Reformation of
interphase array of
microtubules nucleated
by the centrosome.

47. • A dynamic assembly composed of actin &
myosin II filaments called contractile ring.
• actin & myosin II filaments contract to
generate the force that divides the cytoplasm
into two.
• As ring gradually contracts, at the same time
fusion of intracellular vesicles wit the plasma
membrane inserts new membranes.

48. In Plants
• First sign of the plane of division in found in G2
• Circumferential band of microtubules and actin
filaments form a ring around the cell beneath the
plasma membrane.
• This is called Pre prophase band.
• Phragmoplast is formed by overlap of spindle
microtubules at telophase.
• Golgi derived vesicles carrying cell wall precursors
such as cellulose ,pectin etc are associated with
microtubules accumulate in the equatorial region
and fuse to form early cell wall plate.

49. • The plate expands outward by further vesicle
fusion until it reaches the plasma membrane
of the mother cells.

50. Significance Of Mitosis
• Zygote development to Adult.
• Growth & Development of living Organisms.
• Formation of new organs.
• Repair mechanishm.
• Asexual Propagation of Vegetatively
propagated crops.
• Purity of types.

51. Meiosis
• The term meiosis was coined by J.B. Farmer in
1905.
• Derived from Greek word Meioum = diminish or
reduce.
• Division occurs in sexual reproduction.
• The cells that undergo meiosis are called
meiocytes.
• First division of meiosis results in reductionof
chromosome number to half and is called
reduction division/Heterotypic division.

52. • It consists of Meiosis I & Meiosis II
• Meiosis I has
Prophase I
a. Leptotene/Leptonema
b. Zygotene/Zygonema
c. Pachytene/Pachynema
d. Diplotene/Diplonema
e. Diakinesis
Metaphase I
Anaphase I
Telophase I
• Meiosis II is similar to mitotic division.

53. Synaptonemal Complex
•Described by Moses (1956).

55. Recombination Nodule
• Double stranded DNA breaks seem to be induced
by the meiotic endonuclease called Spo 11.
• At Diplotene Chiasma contains a piece of SC.
• This region forms a Recombination nodule.
• Early Nodules, present before pachytene and are
thought to be the site of the recombination
process.
• Late nodules, are present during pachytene and
are thought to be site where initial strand
exchange events being solved as a stable crossing
over.

56. Prophase-1
• It is of a very long duration and is also very
complex.
• Starts with the increase in volume of the
nucleus.

57. Leptotene (Slender Thread)
• Preleptotene :Chromosomes are extremely
thin, long, uncoiled, longitudinally single and
slender thread like structure.
• Leptotene : Chromosomes starts condensing.
The bouquet formation may occur due to the
attachement of ends to the nuclear
membrane.
RNA synthesis and proteins

59. Zygotene(Mating Thread)
• Homologous chromosomes
becomes aligned to undergo
pairing in the process called
synapsis and structure is called
Synaptonemal Complex
• Pairing may begin at the
centromere and proceeds
towards the ends-
Procentric pairing
• May begin at the ends and
proceeds towards the
centromere-Proterminal.
• Coiling of chromosomes
continues to produce shorter
chromosomes.

60. Pachytene (Thick Thread)
• Bivalent consists of four
chromatids and is called
tetrad.
• Each chromosome of the
bivalent has one
kinetochore.
• Physical exchange between
adjacent non sister
chromatids is observed as a
X like structure called
chiasmata.
• Homologs are held together
at chiasmata only.
• Breakdown of SC starts.

61. Diplotene
• Long lasting period.
• SC can no longer be observed.
• chiasmata begin to displace along
the length of chromosome and
gradually reach to the end of
chromosome-chiasmata
Terminalization.
• Darlington - electrostatic force is
responsible.
• Swanson - Despiralization of
chromosome.
• Ostergreen- Tension established
by chiasmata themselves.

62. Diakinesis
• Coiling and contraction of
the chromosome
continues.
• Nucleolus disappear.
• Number of Chiasmata
diminishes.
• Homologues are held
together only at their
ends.
• Nuclear envelope
disintegrates.

63. METAPHASE-I
• Chromosomes are mostly condensed.
• Centromeres of a bivalent are connected to
the poles through the spindle fibres.
• Bivalents will migrate to the equator
• The centromeres of bivalents are arranged on
either side of the equator: Co-orientation.
• Movement of bivalents towards the equatorial
plane is known as Congression.

64. Anaphase -I
• The chromosomes in a bivalent move to the
opposite poles.
• Each chromosome possess two chromatids.
• Centromere is first to move to the pole.
Telophase-1
• Nuclear membrane is formed around the
groups of chromosome at the two poles.
• Nucleus and Nucleolus are re-organized.

66. Meiosis-II

67. Significance Of Meiosis
• Maintaining a constant number of
chromosomes in a species.
• Facilitates segregation and independent
assortment of chromosomes and genes.
• Recombination of genes result in generation
of variability.

68. Case Study

73. References
• Gupta, P.K (2013), Cell And Molecular Biology 3rd ed., Rastogi
Publications,Meerut, 17: 287-298. ( Phases of mitosis and meiosis
information).
• Dr. Paul,A (2015), Text Book Of Cell And Molecular Biology 4th ed.,
Arunabha sen Books & Allied (P) Ltd, Kolkata, 28:879-928.
( Molecular mechanism of phases).
• Becker, W.M. Hardin, J. Bertoni , G. Kleinsmith, L. J. ( 2012), The
World Of The Cell 8th ed., Benjamin-Cummings,Redwood city,
Calfornia. 28: 881-928. ( Replication).
• Alberts ,B. Johnson,A. Lewis,J. Roberts,K and Walter,P. (2008),
Molecular Biology Of The Cell 5th ed., Garland Science, Taylor &
Francis Group, New York.17: 1087-1149, 21:1272-1282.( Cdk’s and
Cyclin, APC, SCF, Diagrams).
Article:https://onlinelibrary.wiley.com/doi/full/10.1111/tpj.14056