The document discusses cell cycle regulation and its importance in cell division, DNA replication, and cell growth. It describes the main phases of the cell cycle - interphase (consisting of G1, S, and G2 phases) and the M phase. Key events in each phase are outlined. The cell cycle is tightly regulated by cyclins and cyclin-dependent kinases (Cdks) that control progression through the cycle. Extracellular factors like growth factors and mitogens also influence cell cycle regulation through cell surface receptors and intracellular signaling pathways.

1. Cell cycle and Growth
regulation
By
Archana. B
Ist yr PG

2. •Cell is the fundamental structural and
functional unit of all living organisms.
•Anton Von Leeuwenhoek first saw and
described a live cell.
•Robert Brown later discovered the nucleus.
•The invention of the microscope and
its improvement leading to the electron microscope
revealed all the structural details of the cell.

3. Cell division is a very important process in all living
organisms.
During the division of a cell, DNA replication and
cell growth also take place.
All these processes, i.e., cell division, DNA
replication, and cell growth, have to take place in
a coordinated way to ensure correct division and
formation of progeny cells containing intact genomes.
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 cell cycle.

4. Phases of Cell Cycle
The cell cycle is divided into two basic phases:
• Interphase
• M Phase (Mitosis phase)
The interval between the mitotic phase is called interphase and
the non- dividing cells spend most of their lifetime in this phase.
The M Phase starts with the nuclear division, corresponding to
the separation of daughter chromosomes (karyokinesis) and
usually ends with division of cytoplasm (cytokinesis).

5. The interphase, though called the resting phase, is the time during
which the cell is preparing for division by undergoing both cell growth and
DNA replication in an orderly manner.
The interphase is divided into three further phases:
G1 phase (Gap 1)
S phase (Synthesis)
G2 phase (Gap 2)
The cells that do not divide further remain in G1 phase to enter an inactive
stage called quiescent stage (G0) of the cell cycle.

6. G1 Phase
• G1 phase corresponds to the interval between mitosis and
initiation of DNA replication.
• During G1 phase the cell is metabolically active and
continuously grows but does not replicate its DNA.
S phase
• S or synthesis phase marks the period during which DNA
synthesis or replication takes place.
• During this time the amount of DNA per cell doubles, but
the chromosomal number does not increase
G2 Phase
• During the G2 phase, proteins are synthesised in
preparation for mitosis while cell growth continues.

7. This is the most dramatic period of the cell cycle, involving a major
reorganisation of virtually all components of the cell.
Since the number of chromosomes in the parent and progeny cells is the
same, it is also called as equational division.
Mitosis is divided into the following four stages:
•Prophase
•Metaphase
•Anaphase
•Telophase

8. Chromatin
condensation and
nuclear membrane
breakdown.
Sister chromatids
move to the
equator
Pro metaphase

9. Chromosomes line up
Seperation of sister
chromatids

10. Seperation of poles
occurs and nuclear
envelope forms
cytokinesis

11. Functional relevance to periodontium:
•Periodontal tissues consists of several cell types and in various stages of
activity.
•There is a constant need for the periodontal ligament and alveolar bone
to under go remodelling.

12. •When situation demands such as following load application there
must be constant increase in the tissue turn over
•A large proportion of cells are in G0 phase in an un divided phase
where they await instruction before they start dividing.
•When need arises external stimuli can induce cells to move from G0
to G1 phase and there by contribute to increased tissue turnover.

14. •The cell cycle is not an un coordinated series of events that operate
without any regulatory mechanism.
•Regulatory proteins control the rate of cell division by providing stops
that can halt the cell cycles at specific check points.
•In addition there is a feed back signalling mechanism which functions to
arrest or slowdown the processes that control the functioning of these
regulatory proteins.
INTRACELLULAR EVENTS:
Regulation of cell cycle is achieved by two sets of proteins:
Cycline dependent kinases (Cdk)
Cyclines

15. •The Cdk are proteins that phosphorylate select proteins at serine –
threonine residues
•These phosphorylated proteins then donstream the signals that influence
the cell cycle and there by the mitotic process is completed.

17. The other set of proteins that are associated with cell cycle are
cyclines.
They undergo cycle of synthesis and degradation during each cycle of
the cell division.
They act by binding to Cdk proteins and regulate their ability to
phosphorylate target proteins.
Two types of cyclines have been recognized
Mitotic cyclines
G1 cyclines

18. Mitotic
cyclines
bind to Cdk during
G2 and are
required for the
progression of cells
to the M phase
G1
cyclines
bind to the protein
at g1 phase and are
required for the S
phase

19. Mechanism of action;
Mitotic cyclines bind to Cdk proteins
during G2 phase
M- phase promoting factor (MPF)
Activation
Phosphorylation – dephosphorylation
of enzymes
Amplification of the reaction
Initiation of cells into mitosis
Degradation of mitotic cyclines that
leads to cessation of cell mitosis
Positive feedback mechanism
End of metaphase and begining of anaphase

20. •The mechanism of action of the G1 cyclins occur in a
similar manner
•The difference occurs only at the level of their action
•The G1 cyclins bind to the Cdk at the G1 phase and
target series of events that lead to DNA replication

21. Activation of Cdk proteins
•Although the mechanism of action of cyclines are similar the down
stream signals are completely different
•The Cdk complexes that are phosphorylated in the two processes
differ
•The substrate in each phase are phosphorylated in such a way that
the activation of of one protein can influence one specific event

22. •For the full activation of Cdk cyclin complex the cells
require Cdk Activating Kinase (CAK)
•These enzymes activate aminoacids that are in close to
the activation sites of Cdk proteins
•And thus the Cdk proteins become potent enough to
phosphorylate other proteins that are involved in
mitosis.

23. Other proteins involved in the cell cycle are:
•Cdk inhibitory proteins
•Cyclin proteolytic proteins

24. Cdk inhibitory proteins (Cdki)
The Cdki bind to the Cdk protein and cause
conformational change in the three dimensional
structure of the protein
The active sites of these protins are not free for further
interaction and so the Cdk proteins are inactivated

25. Cyclin proteolytic proteins:
Cyclin lysis:
The proteolytic destruction of cyclin causes a stop to the cell cycle
It occurs by a ubiquitin dependent mechanism
Several ubiquitin are added to a specific amino acid sequence in the
cyclin protein
This allows the proteosomes to degrade the cyclines

26. This process if influenced by a protein called ubiqutin ligases
namely SCF and APC
SCF is present constantly through out the cell cycle and
regulats the addition of ubiquitin
APC is expressed only during certain stages in the cell cycle
and are specifically involved in protelysis

27. Extracellular regulation:
In the periodontium the cell cycle is regulated by external stimuli
These stimuli of the periodontium majorly help in the cell division and keeps
in pace with the demands of the extracellular matrix
These stimuli are classified into 3 types
•Mitogens
•Growth factors
•Survival factors

28. Mitogens & Growth Factors:
They assist the cells to divide more rapidly than normal
Important mitogens that are involved in the periodontium are
PDGF,EGF and IGF
Target cells for these molecules are mesenchymal, epithelial and
endothelial cells.
These mitogens act chiefly by the activation of G1Cdk activity
Activation of Cdk occur after the mitogens bind to the cell surface
receptors and activate pathways like the MAPK pathway

29. These factors help in the cell growth as a result of upregulation of
intercellular differentiation Some growth factors can also act as
mitogens

30. Growth factor Receptors:
They are a large group of trans membrane protein with more than 50
members
Receptors are classified into two types
Type 1 – N- terminal outside the cell and C- terminal inside
the cytoplasm side
Type 2- N – terminal on the cytoplasmic side

31. All growth factor receptors are type 1
Growth factors bind to the extra cellular N-terminal domain and
the C terminal usually contain the kinase domain.
 The Receptors with kinase domain may have tyrosine or serine -
threonine kinase activity or no kinase activity at all.

32. These receptors are responsible for
mediating their targetted function and
they bind to their ligands with high
affinity
Some growth factors like FGF and TGF β
also bind to sites with lower affinity

33. Dimerization of the
receptor
auto
phosphorylation of
its cytoplasmic
domains
Activation of its
kinase activity
Binding of other
proteins with larger
number of amino
acids
SH2 and SH3
They become
posphorylated
Activated by
binding to their
growth factor
receptors
Generate second
messengers

34. Survival Factors:
These proteins bind to the Bcl2 proteins and as a result of this binding –
prolongs Apoptosis
That avoids early cell death and increases cellular activity.

41. Various Pathways in periodontal cell signelling:
1. WNT pathway
2. Smad pathway
3. MAPK pathway
4. NF-κB pathway

42. Cell Injury:

43. Cell Death:
•Tissue homeostasis is maintained by the ability of proliferating cells
to synthesize macromolecules after differentiation
•Proliferation results in the formation of sufficient number of cell colonies that are
required for adequate matrix synthesis.
•Unchecked prolferation would result in the
far greater number of cells than that can be
accomodated in the matrix.

44. Two major forms of cell death in humans are
1. Necrosis
2. Apoptosis

46. Necrosis:
Coagulation Necrosis:
This type of cell death occurs as a result of denaturation of protein with in the cell.
Because of the breakdown of various components of the cell.
They commonly are associated with external factors like heat , physical stress etc.
Liquifactive necrosis:
This type is commonly associated with release of hydrolytic and other digestive
enzymes that cause cell destruction.
This type of necrosis is seen in inflammatory conditions.

47. Regardless of the type of necrosis, this process is trigerred by
factors that are present in the external environment of the cell
triggers or activates destructive changes in the cell.
It is a dominanat form of cell death seen during pathological
changes that affect the cell due to infection.

48. Necrosis occurs in various periodontal diseases but the degree of necrosis varies
in different forms of diseases.
Necrotising periodontal disease have been cassified into
1. Acute necrotisimg ulcerative gingivitis
2. Necrotising ulcerative periodontitis.
ANUG occurs as an infection resulting from spirochetes and fusobacterium when
host related factors can aid this process features of ANUG is the formation of
punched out creaters in the creast of the interdental papilla.
Necrotizing ulcerative periodontitis is where the infection leads to attachment
loss, but involves only the gingiva, periodontal ligament and alveolar bone.
Usually this spectrum of diseases result in loss of attachment, and therefore
many ANUG diagnoses may be technically termed NUP, although ANUG is the
term in most common use.

49. Apoptosis:
The cells of a multicellular organism are members of a highly organized
community. The number of cells in this community is tightly regulated—
not simply by controlling the rate of cell division, but also by controlling
the rate of cell death. If cells are no longer needed, they commit suicide
by activating an intracellular death program. This process is therefore
called programmed cell death although it is more commonly called
apoptosis.

52. •Autophagy also kills the cells under certain conditions. These are form of
programmed cell death (PCD) and are called autophagic cell death.
•Autophagy is termed a nonapoptotic programmed cell death with different
pathways and mediators from apoptosis.
•It mainly maintains a balance between manufacture of cellular components
and break down of damaged or unnecessary organelles and other cellular
constituents.
•There are some major degradative pathways that include proteasome that
involves breaking down of most short-lived proteins.

54. CONCLUSION
Cell cycle is an important biological phenomenon
that controls the proliferative activity of cells .
Proliferation is an important part of wound healing
and repair and an important parameter that needs to
be assessed in pathologies that involve aberrent
healing.
Periodontitis eventually occurs as a result of an
imbalance between the invading micro- organisms
and the host response
Proliferative activity as assessed by te estimation
of cellcycle may reflect the state of the
pathological as well as the healing processes in the
periodontium.

55. REFERENCES:
Text book of Biology NCERT
Molecular biology of periodontium– Dr. K.V. Arun
Text book of molecular biology- Dr. Sampathnarayanan
Online reference: Khan’s Acadamy