Cell cycle and it's regulation

1. CELL CYCLE AND ITS
REGULATION
PRESENTED TO- PRESENTED BY-
Dr. ANAND K. PANDEY PRANJAL GHARWAR

2. Cell Cycle
• A cell cycle is an
ordered sequence
of events that
occur in a cell in
preparation for
cell division.
• A cell cycle is the
process through
which cell
replicates and
makes two new
cells.

3. Phases of cell cycle
G1 Phase
I. Cell increase in size
II. Cellular contents are duplicated
S Phase
I. DNA replication
II. Each of the 23 pairs is replicated by the cell
G2 Phase
I. Organelles and proteins develop in preparation for cell division
M Phase
I. Mitosis followed by cytokinesis(cell separation)
II. Formation of two identical daughter cells

4.  G0 Phase
i. In this cells are not
actively preparing to
divide
ii. The cell occur in
quiescent(inactive)
stage
iii. Cells that never or
rarely divide such as
mature cardiac cells
remain in this phase
permanently,
neurons etc.

6. •Cell cycle phase identification is important for the
basic investigation of the growth characterstics of cell
lines, especially in cancer research.
•Methotrexate which induces S phase arrest, most
effective when cells are at the G2-M phase transition
and least effective during latter stages of S phase.

7. Cell Division
• It is a process in which a parent
cell divides, eventually giving
rise to new daughter cells
• Multicellular cell divide to
grow, replenish, and reproduce
while unicellular organism
divide generally to reproduce.
• Cell division takes place in M
phase of cell cycle

8. •Cell division is of two types:-
I. Mitosis
II.Meiosis

10. Mitosis
• Mitosis is a process where a single cell divides into two identical
daughter cells.
• The major purpose of mitosis is for growth and to replace worn out
cells.
• Mitosis is also called equational division because in this the
chromosome replicates and equally distribute into two daughter cells.

11. Stages of mitosis
1. Prophase
2. Metaphase
3. Anaphase
4. Telophase

12. 1. Prophase
• In prophase, the chromosomes in
the nucleus change from loosely
dispersed to becoming more
condensed.
• This change in chromosome
structure makes them easier to
move around the cell
• The chromosome at this stage will
consist of two identical parts called
sister chromatids that stay
connected at the centromere.
• The mitotic spindle, a network of
protein filaments, emerges from
centrioles and chromosome move to
the center of the cell.

13. 2.Metaphase
• It is a process that separates
duplicated genetic material
carried in the nucleus into two
daughter cells.
• The cells chromosome align
themselves in the middle if the
cell through a type of cellular
“Tug of war”.
• The chromosomes which have
been replicated and remained
joined at a central point called
the centromere, are called
sister chromatids.

14. • Prior to metaphase, protein
formation called kinetochores
formed around the centromere.
• Long protein filaments called
kinetochore microtubules
extended from poles on either
end of the cell and attached to
kinetochore.
• During metaphase the
kinetochore microtubules pull the
sister chromatids back and forth
until they align along the equator
of the cell, called the equatorial
plane.
• There is an important checkpoint
in the middle of mitosis,called the
metaphase checkpoint, during
which the cell ensures that it is
ready to divide.

15. 3.Anaphase
• It is shortest phase of mitosis
and takes about two to three
minutes of the whole cell
cycle.
• During this phase centromere
splits and each sister
chromatid have their own
centromere. These sister
chromatids move apart from
one another towards opposite
sides of the cell.
• Anaphase begins abruptly with
the release of the cohesin
linkage that holds the sister
chromatids together at the
metaphase plate.

16. • Metaphase to anaphase transition is triggered by the activation of anaphase
promoting complex(APC).
• This proteolytic complex has two crucial function:-
1. It cleaves and inactivates the M phase cyclin thereby inactivating
M- Cdk.
2. It cleaves an inhibitory protein(securin), thereby activating a protease
called separase. Separase then cleaves a subunit in the cohesin
complex to unglue the sister chromatids. The sisters immediately
separate and are now called daughter chromosomes and move to
opposite poles.

17. • The chromosomes move by two independent and overlapping processes.
• The first is Anaphase A:-
 It is the initial poleward movement of the chromosomes. It is
accompanied by shortening of the kinetochore microtubules at their
attachment to the chromosome and, to a lesser extent, by the
depolymerization of spindle microtubules at the two spindle poles.
 The second process is Anaphase B:-
 It is the separation of the poles themselves, which begins after the sister
chromatids have separated and the daughter chromosomes have moved
some distance apart. Anaphase A depends on motor proteins at the
kinetochore.
 Anaphase B depends on motor proteins at the poles that pull the poles
apart, as well as on motor proteins at the central spindle (the bundles of
antiparallel overlap microtubules between the separating chromosomes)
that push the poles apart

18. Telophase
• In telophase a nuclear envelope
reassembles around each group of
chromosomes to form the two
daughter interphase nuclei.
• Nuclear membrane fragments
associate with the surface of
individual chromosomes and fuse
to reform the nuclear envelope.
• During this process, the nuclear
pore complexes are incorporated
into the envelope
• The nuclear envelope once again
becomes continuous with the
extensive membrane of sheet of
the endoplasmic reticulum.

19. Meiosis
• Meiosis is a process where a
single cell divides twice to
produce four cells containing
half of the original amount of
genetic information.
• These cells are our sex cells-
sperm in males, eggs in
females.
• Meiosis can be divided into
nine stages. These are divided
between the first time the
cell divides(Meiosis I) and the
second time it divides(meiosis
II).

20. Mieosis I

21. Prophase I is divided into 5 stages
1. Leptotene:-Each chromosome becomes condensed and visible.
2. zygotene:-The synaptonemal complex begins to develop between the
two sets of sister chromatids in each bivalent.
3. Pachytene:-crossing over occur and formation of chiasmata is seen.
4. Diplotene:-paired chromosome begins to separate into two pairs of
chromatids.
5. Diakinesis:- Diakinesis stage is characterized by chiasmata
terminalization.

25. Regulation of cell cycle
There are several checkpoints to
control cell cycle at different stages
• The restriction point(R) is located at
G1 and is a key checkpoint.
• Other checkpoints are located at the
transitions between G1 and S, and G2
and M.
• This cell cycle is also regulated by
cyclins which control cell progression
by activating cyclin dependent
kinase(CDK) enzymes

26. REGULATION AT INTERNAL
CHECKPOINTS
1. G1-S CHECKPOINT
2. G2-M CHECKPOINT
3. DURING METAPHASE

27. G1-S Checkpoint
• The G1-S checkpoint determines
whether all conditions are
favorable for cell division to
proceed and for DNA replication
to occur during S phase.
• The G1-S checkpoint, also called
the restriction point, is the point
at which the cell irreversibly
commits to the cell division
process. Cell size and protein
reserves are assessed.
• A cell that does not meet all the
requirements will arrest in G1 and
will attempt to correct these
deficiencies.

28. G2-M Checkpoint
• The G2-M checkpoint bars the entry to the
mitotic phase if certain conditions are not
met.
• The most important role of the G2
Checkpoint is to ensure that all of the
chromosomes have been replicated and
that the replicated DNA is not damaged.

29. During metaphase
• The M checkpoint occurs near the
end of the metaphase stage of
mitosis.
• The M checkpoint is also known as
the spindle checkpoint because it
determines if all the sister
chromatids are correctly attached to
the spindle microtubules.

30. Positive regulation of
the cell cycle
• Two groups of proteins, called cyclins and
cyclins dependent kinases(Cdks),are termed
as positive regulators.
• They are responsible for the progress of the
cell through various checkpoints.
• The levels of cyclins protein fluctuate
throughout the cell cycle in a predictable
manner.
• After the cell moves to the next stage, the
cyclins that were active in the previous stage
are polyubiquitinated and degraded by the
proteosome.

31. • Cyclins regulate the cell cycle only when they are tightly bound to Cdks.
• To be fully active, the Cdk/cyclin complex must also be phosphorylated in
specific locations. Like all kinases, Cdks are kinase enzymes that
phosphorylated in specific locations.
• Phosphorylation activates the protein by changing its shape.

32. Negative regulation of the cell
cycle
• They stop the cell cycle in comparison to positive regulation.
• The best understood negative regulatory molecules are retinoblastoma protein
and p53.

33. 1.Retinoblastoma(Rb)
• These protein are group of tumor suppressor proteins, which function
to prevent tumor growth by inhibiting cell division.
• Rb acts primarily the G1-S checkpoint. Rb, which largely monitors cell
size, exerts its regulatory influence on the other positive regulator
proteins.
• In the active dephosphorylated state, Rb binds to proteins called
transcriptional factors, most commonly, E2F.
• Transcriptional factors turn on specific genes, allowing the production
of proteins encoded by the gene.
• When Rb is bound to E2F, the production of proteins necessary for
the G1/S transition is blocked.

36. p53
• If damaged DNA is detected
at any checkpoint, activation
of the checkpoints result in
increased p53 protein
production
• p53 is a tumour suppressor
gene that stops progression
of the cell cycle and starts
repair mechanism for the
damaged DNA
• If this DNA cannot be
repaired, it ensures the cell
undergoes apoptosis and
can no longer duplicate.
1TUPTUMOR SUPPRESSOR P53 COMPLEXED WITH DNAPDB
DOI: 10.2210/pdb1TUP/pdbNDB: PDR027

37. References
• https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6663871/#:~:text=C
ell%20division%2C%20or%20mitosis%2C%20is,metaphase%2C%20an
aphase%2C%20and%20telophase.
• Campbell biology
• Alberts molecular biology
• https://www.genome.gov/genetics-glossary/Cell-
Cycle#:~:text=A%20cell%20cycle%20is%20a,mitosis%2C%20and%20c
ompletes%20its%20division
• https://www.britannica.com/science/cell-cycle