1. CELL CYCLE
Presented by:
Mr. S. KONMEI MUKHOLEE
M.Sc. 2nd semester 2017
DEPARTMENT OF LIFE SCIENCE
Bangalore university
Dr . Hari Prasad T.N.P
Assistant professor
DEPARTMENT OF LIFE SCIENCE
Bangalore university
Guided by:
2. CELL CYCLE
• 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 two
identical daughter cells.
• 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:
INTERPHASE and MITOSIS.
• The duration of cell cycle varies from hours to
years. A typical human cell has a duration of 24
hours.
Fig: Over view of Cell cycle
3. PHASES OF CELL CYCE
It consists of 2 major activities.
G1 (pre-synthetic phase)
S (DNA synthesis)
G2 (pre-mitotic phase)
INTER PHASE
It includes division of the cell nucleus
(mitosis) and division of the cell cytoplasm
(cytokinesis)
MITOSIS (M PHASE)
4. INTERPHASE
It is the longest phase.
In a typical human cell out of 24hrs,
interphase last for 23hrs.
It is also known as resting phase of the cell
cycle.
During this phase mRNA and rRNA are
synthesized. The chromosomes duplicates
into two chromatids.
The centrospheres of centrioles and
microtubules arise.
Stage of interphase
Interphase consists of 3 sub-stages
G1 PHASE
S PHASE
G2 PHASE
5. also called as cell differentiation
In this phase cell quit from cell cycle hence also called as
phase of cell quiescence
In these cells cyclin D is in decreased concentration.
Rb protein is in hypo-phosphorylated (active form).
GO PHASE
G1 PHASE (first gap)
It is also called the growth phase.(longest phase)
During this phase 20 amino are formed, from which millions
of proteins and enzymes are formed, which are required in S
phase.
Cell is preparing for S phase
During this phase mRNA, rRNA and tRNAs are formed.
Concentration of cyclin D increases.
Formation of cyclin E complex is necessary.
6. During this phase DNA synthesis occurs.
histone synthesis
Cyclin E/CDK and cyclin A/CDK regulate the processes in
phase S.
Cyclins, when bound with the dependent kinases such asCdk1
proteins form the Maturation- Promoting Factor (MPF).
S PHASE (DNA synthesis)
It is the second growth phase.
Cells continue to grow and produce new proteins.
The nucleus increases in volume.
mRNA, tRNA and rRNA synthesis also occur. This phase has
double the number of chromosomes.
Cyclin A/cdk and cyclin B/cdk complexes are active which
are necessary for the cell to enter into M phase (check point 2).
G2 PHASE (pre-mitotic phase)
8. CELL CYCLE CHECKPOINTS (RESTRICTION POINTS)
1.G1checkpoint (G1restriction point)
2.G2 checkpoint.
3.M checkpoint.
A checkpoint is a stage in the eukaryotic cell cycle at which the cell examines internal
and external cues and "decides" whether or not to move forward with division.
9. G1 checkpoint (G1restriction point)
It prevents DNA damage from being replicated.
This restriction point is mainly controlled by the action of the
CDKI-p16 (CDK inhibitor p16). The inhibited CDK not bind
with cyclin D1, hence there is no cell progression.
Active cyclin D-cdk complexes phosphorylate retinoblastoma
protein (pRb) in the nucleus.
Once pRb gets phosphorylated, E2F activates the transcription
of cyclins E and A, which then interacts with CDK2 to allow
for G1-S phase transition.
G1 checkpoint
Checks for;
Cell size
Nutrients
Growth factor
DNA damage
10. G2 checkpoint
This checks the number of factors which are essential for the cell division.
MPF (Maturation-promoting factor) promotes the G2 phase into the
entrance of M-phase.
The main functions of MPF in this restriction point are :
Triggers the formation of mitotic spindle.
Promotes chromosome condensation.
Causes nuclear envelop breakdown.
If there are any damages are noticed in this restriction point, then the
phosphatase not activate the MPF, resulting in the arrest of cell cycle in G2
phase till the repair of the damaged DNA.
11. M checkpoint
It is also known as spindle checkpoint.
This occurs at metaphase.
Anaphase-promoting complex (APC) regulates this
checkpoint.
Check whether the sister chromatids are correctly
attached to the spindle microtubules
If there are mistakes then it delays the cell in entering
into anaphase from metaphase.
12. What happens if you lose one of checkpoints?
DNA replication and chromosome distribution are indispensable events in
the cell cycle control. Cells must accurately copy their chromosomes, and
through the process of mitosis, segregate them to daughter cells.
The checkpoints are surveillance mechanism and quality control of the
genome to maintain genomic integrity.
Checkpoint failure often causes mutations and genomic arrangements
resulting in genetic instability.
Checkpoint studies are very important for understanding mechanisms
of genome maintenance as they have direct impact on the ontogeny of birth
defects and the cancer biology.
13. CYCLINS
. The cyclin in the mammalian are roughly divided
according to their activity in the different phase of the
cell cycle.
The G1/S cyclin includes the D and E type cyclin.
The M phase specific cyclin includes the B type
cyclins.
Cyclin of type A are active in S, G2 and M phase
CELL CYCLE REGULATORS
cyclin D
cyclin Acyclin E cyclin BCyclin are basically some protein which helps in cell
cycle regulation with their partner CDKs.
Cyclin of type D, A, E and B shows characteristic
concentration change in the course of cell cycleFunction of cyclin:
Activation of CDK.
contribution to substrate specificity of CDKs.
Regulation of cyclin expression.
14. The attached phosphate group acts like a switch, making
the target protein more or less active.
When a cyclin attaches to a Cdk, it has two important
effects:
it activates the Cdk as a kinase, but it also directs the Cdk
to a specific set of target proteins,
G1/S cyclins send Cdks to S phase targets (e.g., promoting
DNA replication)
M cyclins send Cdks to M phase targets (e.g., making the
nuclear membrane break down).
How does this work?
PHASE CYCLIN CDK
GO C CDK3
GI D,E CDK4, CDK2,
CDK6
S A,E CDK2
G2 A CDK2, CDK1
M B CDK I
CDKs( Cyclin Dependent Kinases)
CDKs are kinases, enzymes that phosphorylate (attach
phosphate groups to) specific target proteins.
15. Cancer and the cell cycle
Cancer cells may make their own growth factors
Cancer cells can divide many more times than this,
largely because they express an enzyme
called telomerase.
cancer cells gain the ability to migrate to other parts of
the body, a process called metastasis, and to promote
growth of new blood vessels, a process
called angiogenesis (which gives tumor cells a source of
oxygen and nutrients).
Cancer is basically a disease of uncontrolled cell division. Its development and progression are usually
linked to a series of changes in the activity of cell cycle regulators.
How cancer develops?
Most cancers arise as cells acquire a series of mutations
If a cell lose the activity of a cell cycle inhibitor = form BENIGN TUMOR
Increased activity of a positive cell cycle regulator in one of the descendants
cells may give rise to MALIGNANT TUMOR
16. Cell cycle regulators and cancer
Mutations of two types of cell cycle regulators may promote the development of cancer: positive regulators may
be overactivated (become oncogenic), while negative regulators, also called tumor suppressors, may be
inactivated.
ONCOGENES
The overactive (cancer-promoting) forms of these genes are
called oncogenes, while the normal, not-yet-mutated forms are
called proto-oncogenes.
Mutations that turn proto-oncogenes into oncogenes can take
different forms
. change the amino acid sequence of the protein.
Amplification or an error in DNA repair.
the growth factor receptor, the Ras protein, and the signalling enzyme
Raf are all encoded by proto-oncogenes.
Overactive forms of these proteins are often found in cancer
cells. oncogenic Ras mutations are found in about 90% of
pancreatic cancers.
Cancer-causing mutations often change Ras’s structure so
that it can no longer switch to its inactive form, or can do
so only very slowly, leaving the protein stuck in the “on”
state.
17. TUMOR SUPPRESSORS
Genes that normally block cell cycle progression are known as tumor suppressors.
Tumor suppressors prevent the formation of cancerous tumors when they are working correctly, and tumors
may form when they mutate so they no longer work.
One of the most important tumor suppressors is tumor protein p53
When a cell’s DNA is damaged, a sensor protein
activates p53, which
halts the cell cycle at the G1, checkpoint by
triggering production of a cell-cycle inhibitor
activate DNA repair enzymes
triggering apoptosis (programmed cell death) so
that damaged DNA is not passed on.
In cancer cells, p53 is often missing, non
functional, or less active than normal.
For example, many cancerous tumor have a mutant
form of p53 that can no longer bind DNA. When
p53 is defective, a cell with damaged DNA may
proceed with cell division.
18. APOPTOSIS VS. NECROSIS
• usually “spill their
guts” as they die.
• the cell swells up.
• Causes
inflammation in the
tissue.
• They shrink and develop
bubble-like protrusions
(“blebs”) on their surface.
• the DNA in the nucleus
gets chopped up into small
pieces, and some
organelles of the cell, In
the end, the entire cell
splits up into small chunks.
Necrosis (the messy way)
Apoptosis is a form of programmed cell death, or “cellular suicide.”
Greek word “apo” meaning “away” and “ptosis” meaning “falling”.
APOPTOSIS
Apoptosis (the tidy way)
19. In order to remove cells that should no longer be part of the organism.
•Some cells need to be “deleted” during development.
•Abnormal cells
•Cells in an adult organism may be eliminated to maintain balance.
Apoptosis is part of development:
Why do cells undergo apoptosis?
in the worm C. Elegans, 131 cells will die by apoptosis as the worm develops from a
single cell to an adult.
Apoptosis also plays a key role in human development.
Other examples of apoptosis during normal development include the loss of a
tadpole’s tail as it turns into a frog.
20. Apoptosis is key to immune function:
development and maintenance of a healthy immune system.
Apoptosis also plays an important role in allowing the immune
system to turn off its response to a pathogen.
Apoptosis can eliminate infected or
cancerous cells:
When a cell’s DNA is damaged, it will typically detect
the damage and try to repair it.
21. REFERENCE:
A Textbook Of “Cell And Molecular Biology” Author SP Vyas, A Mehta First
Edition 2011,CBS Publishers & Distributors Pvt. Ltd.
A textbook of “Genetics” Author P.S VERMA ,V.K AGARWAL 9th Revised Multicolour
First Edition 1975. Printed Rajendra Ravindra printers Pvt.Ltd; Published by S CHAND &
COMPANY Pvt.Ltd
A text book of “cell biology” Author T DEVASENA First edition April 2012 publisher;
OXFORD UNIVERSITY PRESS.
‘’Cell Biology, Genetics, Molecular Biology, Evolution & Ecology’’ Author P.S VERMA., V.K.
AGARWAL Publisher: S Chand; Reprint Edition. 2006 edition (1 September 2004)