The cell cycle is regulated by cyclins and cyclin-dependent kinases (Cdks). Cyclins activate Cdks to phosphorylate proteins and trigger transitions between phases such as G1 to S and G2 to M. Checkpoints ensure completion of earlier steps before progression. The levels of cyclins and activity of Cdks are regulated by other proteins in response to internal signals, like DNA replication status, and external signals, like growth factors, to control the cell cycle.

1. Regulation of mitotic cell cycle in
eukaryotes

2. contents
 Introduction
 Cell cycle
 The phases of mitotic cell cycle
 Regulation of the cell cycle
 Check points of the cell cycle

3. Introduction
• We have previously seen that prokaryotic replication can be
regulated by preventing initiation complex formation .
• Since eukaryotic replication is quite a bit similar to the
prokaryotic replication , it is expected that control of
initiation will play a role in the eukaryotes too.
• However , regulation here must be considerably more
complex not only because eukaryotic chromosomes have
several replicons, but also – and probably more importantly
so- because the cell cycle in eukaryotes in much much more
complex.
• As one considers the process of mitosis, keep in mind that
the structural and functional changes are regulated by the
cell cycle machinery.

4. Cell cycle
Defination :- when the cell has grown to its
maximum size it divides , and it take place a series
of changes in a newly formed cell which involve in
growth and division to form 2 daughter cells, it is
called cell cycle.
It consist of two stages,
1. A non dividing growing interphase
2. A short dividing mitotic / M phase

5. The phases of mitotic cell cycle
 The period between 2 mitotic division is called Interphase.
 It is further divisible into 3 stages:
1. G1 phase
2. S phase
3. G2 phase
 G1 phase:- It is post mitotic phase and takes place at the
end of cell division the newly formed cells accumulate the
energy and prepares themselves for the synthesis of DNA.
 During this, active synthesis of RNA and protein takes place.

7. S phase :- It is the synthesis phase during this phase
duplication of DNA and centriol takes places.
The duplication of DNA results in the duplication of
chromosomes.
G2 phase:- It is the pre-mitotic gap phase (invisible
phase) the synthesis of RNA and protein continues in
this phase.
The formation of macro molecules for spindle
formation takes place and the cell prepare itself to go
into the mitotic phase.

8. Mitotic phase
• M phase follows the interphase. This last for a short
period compare to interphase.
• During this phase 2 important processes occur
simultaneously they are,
Karyokinesis (division of nucleus): It results in the
separation of chromosomes into 2 equal groups.
Cytokinesis (division of cytoplasm):- It results in
division of cytoplasmic components into
approximately 2 halves.
• After M phase a cell may either enter interphase to
repeat the cell cycle or G0 phase to arrest the cell
cycle.
• The cells in G0 phase may grow in size and get
differentiated.

9. Regulation of the cell cycle &
checkpoints
• Mitotic chromosome cycle is found to be regulated
by the following 3 control factors :
1. The S –phase activator that normally appears in
the cytoplasm only during S –phase and ‘switches
on ‘ DNA synthesis (Rao and Johanson ,1970).
2. The M-phase promoting factor (MPF) that is
present only in M-phase cytoplasm and causes
chromosomes condensation .
3. The DNA- dependent M-phase delaying factor
that is present in S-phase cytoplasm and inhibits
the process leading to onset of MPF production.

10. • Each successive step depends on a preceding one (all
processes of chromosomes cycle are linked together as
dependent sequence).Thus,
1. The cell can not pass through mitosis until MPF has been
produced
2. MPF cannot be produced until M-phase –delaying factor
has disappeared
3. The M-phase delaying factor and S –phase activator cannot
disappear until DNA – synthesis has ended
4. DNA synthesis cannot end until all of the DNA has
replicated
5. The DNA cannot begin to replicate until DNA re-replication
block has been removed by passage through mitosis into
G1 and lastly
6. A cell cannot progress from mitosis into G1 , until the
chromosomes have separated on the mitotic spindle.

12. A check point in the cell cycle is a critical control point
where stop and go signals regulate the cycle.
3 major checkpoints are found in the G1, G2, and M
phases.
G2 checkpoint control by MPF
Active MPF(Maturation promoting factor) = mitotic
Cdk + mitotic cyclin
Cdk is cyclin –dependant kinase
MPF controls G2 → phosphorylating and activating
proteins involving in :-
• chromosome condensation
• Nuclear envelope breakdown
• Spindle assembly

14. • The cell cycle is regulated by protein kinases.
• The mechanism regulating the progression of cells
through their division cycle is highly conserved in
evolution, and plants have retained the basic
components of this mechanism.
• The key enzymes that control the transitions
between the different states of the cell cycle, and
the entry of nondividing cells into the cell cycle,
are the cyclin-dependant protein kinases,or CDKs.
• Endogenous hormones such as auxin, cytokinins,
abscisic acid, gibberellins and brassinosteroids as
well as enviornmental factors all regulate
progression through the cell cycle.

15. • Protein kinases are enzymes that phosphorylate
proteins using ATP.
• The regulated activity of CDKs is essential for the
transitions from G1 to S and from G2 to M, and for
the entry of nondividing cells into the cell cycle.
• The transition from G1 to S requires a set of cyclins
(G1 cyclins ) different from those required in the
transition from G2 to mitosis, where mitotic cyclins
activate the CDKs.

16. • Similarly, protein phosphatases can remove
phosphate from CDKs, either stimulating or
inhibiting their activity, depending on the position
of the phosphate.
• CDK activity can be regulated in various ways, but
2 of the most important mechanisms are
1. Cyclins synthesis and destruction and
2. The phosphorylation and dephosphorylation of
key amino acid residues within the CDK protein.

17. Summary : - Cell cycle control
A “clock” is running within the cell – of synthesis
and degradation of cyclins- which activate cyclin-
dependate kinases (Cdk’s ) which activate other
proteins to causes checkpoints transitions.
The “clock” is adjusted (cyclins and Cdk’s are
regulated ) by other proteins, based on :
External signals (growth factors )
Internal signals (correct completion of previous
step )

18. REFERENCES
cell biology, genetics , molecular biology,
evolution and ecology :- P.S VERMA & V.K.
AGARWAL
https://wikipedia.com
https://slideshare.com