CELL CYCLE AND CHECKPOINTS

1. CELL CYCLE AND REGULATION
SUBMITTED BY :- AKSHIT GHAI
SUBMITTED TO :- DR. GINJINDER KAUR
CLASS:- M.Sc. HUMAN GENETICS SEM2
ROLL NO :- 20211014
UNI ROLL NO:- 62822

2. CELL CYCLE
1. The cell cycle is an ordered series of
events by which cell duplicates its genome
and eventually divides into two daughter
nuclei
2. The cell cycle has 2 main phases :-
INTERPHASE AND M-PHASE.
3. INTERPHASE is further divided into 3
stages :- G1 phase , S phase and G2 phase.
4. Cells that do not divide enters into G0
state.
5. Approx. 95% of the cell cycle is spent in
interphase.
6. Time spent by a typical proliferating
human cell in G1 phase is 11 hours , S
phase is 8 hours and G2 phase is 4 hours
and M phase is 1 hour.
7. Dna content 2C doubles to 4C, however
there is no increase in chromosomes
number 2n.

3. EXTRACELLULAR SIGNALS
GOVERN CELL CYCLE
ENTRY
1. Various cell signaling pathways that
contribute to the cell cycle initiation like
GPCR , RTK , wnt Signalling , mTOR ,
cytokine pathway etc.
2. Cell proliferation is controlled by the
presence of growth-promoting factors
(mitogens) and growth-inhibiting factors
(anti-mitogens) in the cell surroundings.
3. Mitogens activate the transcription of
multiple genes
4. Many genes activate transcription
factors, such as c-Fos and c-Jun, Myc
induces the transcription of G1 cyclin
and CDK genes. That will lead to cell
cycle progression

4. CHECKPOINTS
• They ensure incomplete or
damaged chromosomes are not
replicated.
• It ensures the fidelity of cell
division
• There are 4 checkpoints:-
• G1 checkpoint at G1/S
transition
• Intra S phase checkpoint
• G2 checkpoint at G2/M
transition
• The spindle assembly
checkpoint (SAC) at Metaphase
to anaphase transition.

5. CELL CYCLE PROGRESSION
• The engine that drives the cell cycle is a series of
protein complexes composed of 2 subunits :-
CYCLIN and CDKs.
• There are 4 classes of cyclins G1- cyclins, G1/S-
cyclins, S- cyclins and M- cyclins.
• Regulation of activity of Cyclin-CDK complex is
done by phosphorylation/dephosphorylation and
CKIs (INK4 family and 3 protein family:- p21CIP
p27KIP1 p57KIP2)
• Level of cyclin changes but CDKs Remain constant.

6. G1 checkpoint
1. Growth factors stimulate and sustain
the G1 cyclins- CDK activity
2. The resulting cyclin D–CDK4/6
complexes begin phosphorylating Rb.
3. Releasing some E2F which
stimulates transcription of the genes
encoding cyclin E, CDK2, and E2F
itself.
4. The cyclin E–CDK2 complexes
further phosphorylate Rb resulting in a
positive feedback loop
5. Once G1/S phase CDKs are
sufficiently high, cells pass through the
restriction point.
6. Cells are committed irreversibility to
division at a cell cycle point, if they
pass it, called Restriction point.
7. They commence DNA replication and
centrosome duplication.

7. What happens when error is found by G1
checkpoint
1. When there is any error found , the
ATM protein is recruited by the DDR
(DNA damage response) due to Double
stranded breaks in dna
2. Chk2 is activated which phosphorylate
p53 and stabilizes, thus no
degradation occurs.
3. When no DNA damage, p53 is
unphosphorylated , and binds to MDM2
which marks it for proteosomal
degradation.
4. p53 transcribes p21 which inhibits
cyclin E – cdk2 complex

8. Intra S phase checkpoint
1. Occurs in the S phase of the cell cycle
2. It ensures the chromosomes are replicated
and the replicated DNA of the cell is not
damaged before entering mitosis.
3. Mitotic cyclin B accumulates gradually and
binds to CDK1.
4. When cyclin B binds to CDK1, the resulting
complex is known as MPF4.
5. This complex acts as the signal for the G2
cell to enter mitosis and induce:
6. Condensation of chromosomes,
7. Nuclear envelope breakdown,
8. Assembly of the mitotic spindle, and
9. Alignment of condensed chromosomes at
the equatorial region.
Tyrosine Threonine

9. What happens when error is found by intra
S checkpoint
1. As seen in previous checkpoint
ATM/ATR is activated due to errors in
DNA replication
2. Resulting in chk1/2 activation
3. Inhibition of cdc25A
4. Thus no activation of M phase
cyclins-cdk complex, resulting in
halting of cell cycle

10. G2 checkpoint

12. Spindle assembly checkpoint
1. Also known as M phase checkpoint
2. Prevents separation of duplicated
chromosomes until correct attachment
of spindle fibers is achieved, also
monitors the alignment of chromosomes
on the metaphase plate
3. It is between the transition from
metaphase to Anaphase.
4. Activity of APC/C (anaphase promoting
complex / cyclosome) is regulated by
this checkpoint.
5. SAC prevents premature activation of
APC/C

13. 6. The unattached kinetophore is
bounded by proteins which causes
the activation of cytoplasmic
proteins forming MCC (Mitotic
checkpoint complex).
7. MCC will bind to APC/C thus
making it inactive
8. APC/C inhibition results in
halting of cell at metaphase stage
WHAT HAPPENS WHEN APC/C IS
ACTIVE
1. APC/C will degrade securin
2. This will lead to ubiquitin
degradation of seperase
3. Thus seprated chromatids
moves to other ends in
anaphase

14. THANK YOU