Presented by: Srishti Aggrawal Dept of Science. DEI,AGRA

1. CELL CYCLE AND ITS
CHECKPOINTS
 PRESENTED BY :
SRISHTI AGGRAWAL
 M.SC BOTANY
 DEPT.OF SCIENCE
 DEI,AGRA
 PRESENTED TO :
AJAY KUMAR
 PROFESSOR
 DEPT.OF SCIENCE
 DEI,AGRA

2.  Definition
 Different phases of cell cycle
 Various checkpoints
 Growth factors that effect cell cycle
◦ Positive regulators
◦ Negative regulators
CONTENTS

3.  A cell cycle is a series of events that a cell passes
through from the time until it reproduces its replica.
 It is the growth and division of single cell into daughter
cells and duplication (replication).
 In prokaryotic cells, the cell cycle occurs via a
process termed binary fission.
 In eukaryotic cells, the cell cycle can be divided in two
periods-
a) interphase
b) mitosis
CELL CYCLE

5. It consists of 2 major activities.
◦ INTER PHASE
G1 (pre-synthetic phase)
S (DNA synthesis)
G2 (pre-mitotic phase)
◦ CELL DIVISION (MITOTIC PHASE)
a) Interphase- During this phase the cell grows, accumulating
nutrients needed for mitosis and duplicating its DNA.
b) Mitosis (M)-phase- During which the cell splits itself into two
different cells.
The duration of the cell cycle varies from hours to years. A
typical human cell has duration of 90h.
PHASES OF CELL CYCLE

6. A) INTERPHASE: It is the longest phase. In a typical human cell, out of
the 90h, interphase lasts for 89h.
CHARACTERS OF INTERPHASE: It is the resting phase of the cell.
Resting refers to the rest from division. But, the cells in the interphase
are metabolically active. The metabolic activities are high in this phase.
The cell grows during phase. During this phase mRNA and rRNA are
synthesized. The chromosomes duplicates into two chromatids. The
centrioles duplicates into two. Thus two centrioles are formed. The
centrospheres of centrioles, microtubules arise.These microtubules
form asters.
STAGES OF INTERPHASE: Interphase consists of 3 sub-stages.
They are :
1. G1 phase
2. S phase
3. G2 phase
INTERPHASE

7. G1 phase : It is the 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.
 During G1, a lot of protein synthesis happens in order to increase
the amount of cytosol in the cell. The increase in cell size
happens in this stages.
S phase : It is the synthesis phase during this phase duplication
of DNA and centriole 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 .

9. G2 cells are divided into two daughter cells which may enter the cycle
again at G1 phase or come out of the cycle to G0 phase.
Mitosis is the distribution of the two sets of chromosomes into two separate
and equal nuclei.
This is the division phase. During this phase the cell divides. This phase
has a short duration. A typical human cell cycle has duration of 90h. Of these
the M phase has duration of 45 to 60min. This phase has two sub-phases
called karyokinesis and cytokinesis.
Karyokinesis refers to the cell division of nucleus into two daughter nuclei.
It has 4 sub-stages, namely prophase, metaphase, anaphase and telophase.
Cytokinesis refers to the cell division of the cytoplasm resulting in two
daughter cells.
MITOSIS IS DIVIDED INTO FIVE PHASES :
1) Pro phase- mitotic spindle formation
2) Meta phase- metaphase plate
3) Ana phase- mitotic apparatus
4)Telo phase- cytokinesis
M PHASE (MITOSIS)

10. REPRESENTATION OF MITOSIS
STAGES

11. 1) STUDIES OF FROG OOCYTE.
2) GENETIC ANALYSIS OF YEAST- Saccharomyces
cerevisiae
3) STUDIES OF PROTEIN SYNTHESIS IN EARLY SEA
URCHIN EMBRYO.
THREE EXP. USED TO STUDY CELL
CYCLE REGULATION

12. These are the cell cycle control mechanisms in eukaryotic
cells. These checkpoints verify whether the processes at each
phase of cell cycle have been accurately completed before
progression into the next phase. There are three main
checkpoints that control the cell cycle in eukaryotic cells.
They are –
1. The G1 checkpoint,at the G1/S transition.
2. The G2 checkpoint,at the G2/M transition.
3. The spindle checkpoint, at the transition from metaphase
to anaphase.
CELL CYCLE CHECKPOINTS

13. .
CHECKPOINTS

14.  At the G1 checkpoint, a cell checks whether internal and external
conditions are right for division. Here are some of the factors a
cell might assess:
• Size. Is the cell large enough to divide?
• Nutrients. Does the cell have enough energy reserves or
available nutrients to divide?
• Molecular signals. Is the cell receiving positive cues (such as
growth factors) from neighbours?
• DNA integrity. Is any of the DNA damaged?
If a cell doesn’t get the go-ahead cues it needs at the
G1 checkpoint, it may leave the cell cycle and enter a resting state
called G0 ​ phase. Some cells stay permanently in G0, while others
resume dividing if conditions improve.
G1 CHECKPOINT ( G1 restriction point)

15.  To make sure that cell division goes smoothly (produces healthy
daughter cells with complete, undamaged DNA), the cell has an
additional checkpoint before M phase, called the G2 checkpoint. At
this stage, the cell will check:
• DNA integrity. Is any of the DNA damaged?
• DNA replication. Was the DNA completely copied during S phase?
 If errors or damage are detected, the cell will pause at the G2
checkpoint to allow for repairs. If the checkpoint mechanisms detect
problems with the DNA, the cell cycle is halted, and the cell attempts
to either complete DNA replication or repair the damaged DNA.
 If the damage is irreparable, the cell may undergo apoptosis, or
programmed cell death. This self-destruction mechanism ensures that
damaged DNA is not passed on to daughter cells and is important in
preventing cancer.
G2 CHECKPOINT

16. This occurs at metaphase.
Anaphase-promoting complex (APC) regulates this
checkpoint .This is also called spindle checkpoint.
This checks whether all chromosomes are properly attached
to the spindle or not. This also governs the alignment of the
chromosomes and integrity of the spindles. If there are
mistakes then it delays the cell in entering into anaphase from
metaphase.
METAPHASE CHECKPOINT

17. The cell cycle is regulated by cycles.
1. Cyclins
2. Cyclin-dependent kinases (CDKs)
3. Cyclin-dependent kinase inhibitors (CDKIs).
1. CYCLINS:
• Their concentration varies during the cell cycle. Cyclins are the family of
proteins which regulates the cell cycle.
• There are several types of cyclins that are active in different parts of the cell
cycle and causes phosphorylation of CDK.
There are four basic types found in humans and most other eukaryotes:
G1cyclins, G1/S cyclins, S cyclins, and M cyclins.
 As the names suggest, each cyclin is associated with a particular
phase, transition, or set of phases in the cell cycle and helps drive the
events of that phase or period. For instance, M cyclin promotes the
events of M phase, such as nuclear envelope breakdown and
chromosome condensation
CELL CYCLE REGULATORS

18. The levels of the different cyclins vary considerably across
the cell cycle, as shown in the diagram at right. A typical
cyclin is present at low levels for most of the cycle, but
increases strongly at the stage where it's needed. M cyclin,
for example, peaks dramatically at the transition from G2 to
M phase. G1 cyclins are unusual in that they are needed for
much of the cell cycle.

19. CYCLIN CDK PARTNER FUNCTION
A CDK2,CDK1 S,G2 PHASE
B CDK1 M PHASE
D1 CDK4,CDK6 G1 PHASE
D2 CDK4,CDK6 G1 PHASE
D3 CDK4,CDK6 G1 PHASE
E CDK2 G1 ,S PHASE
C CDK8 TRANSCRIPTION
F G2,M PHASE
G P53 RESPONSIVE
H CDK7 CAK, TRANSCRIPTION

20. CYCLIN-DEPENDENT KINSASES (CDKS)
• These are a family of protein kinases that regulates the cell cycle.
They are present in all known eukaryotic cells.
In order to drive the cell cycle forward, a cyclin must activate or inactivate
many target proteins inside of the cell. Cyclins drive the events of the cell cycle
by partnering with a family of enzymes called the cyclin-dependent
kinases (Cdks). A lone Cdk is inactive, but the binding of a cyclin activates it,
making it a functional enzyme and allowing it to modify target proteins.
PHASE CYCLIN CDK
G0 C CDK3
G1 D,E CDK4 , CDK2 , CDK6
S A,E CDK2
G2 A CDK2, CDK1
M B CDK1

21. CYCLIN-DEPENDENT KINASE INHIBITORS
(CDKIS)
• CDKI is a protein which inhibits cyclin-dependent kinase (CDK).
• Cell cycle progression is negatively controlled by cyclin-dependent
kinases-inhibitors (called CDIs, CKIs or CDKIs).
• These are involved in cell cycle arrest at the G1 phase.
CDK I INTERACTING CDK
p 16 CDK 4, CDK6
p 15 CDK4
p 18 CDK4, CDK6
p 19 CDK4, CDK6
p 21 CYCLIN E1, CDK2
p 27 CDK3, CDK4, CDK2,CYCLIN E1
p 57 CYCLIN E1, CDK2

22. Are those which control the changes necessary for cell
division.
They include:-
◦ Cyclins
◦ Cyclin-dependent kinases(cdks)
POSITIVE REGULATORS

23. Are those which control the positive regulators.
They include :-
◦ Rb proteins
◦ P53 gene
◦ Inhibitors of cdks - which are of 2 types
Ink family (Inhibitors of kinases)
P19 ,P15
CIP family (cdks inhibitory proteins)
P21, P57
NEGATIVE REGULATORS

24. DNA damage leads to the activation of the gene regulatory
protein p53, which stimulates the transcription of several
genes.
One of these encodes a CKI proteins p21, which binds to
G1/S-Cdk and S-Cdk and inhibits their activites, thereby
helping to block entry into S phase. In a normal cell p53 is
inactivated by its negative regulator, mdm2. Upon DNA
damage or other stresses, various pathways will lead to the
dissociation of the p53 and mdm2 complex. Once activated,
p53 will induce a cell cycle arrest to allow either repair and
survival of the cell or apoptosis to discard the damaged cell.
How p53 makes this choice is currently unknown.
p53 PROTEIN