• All multicellular organisms originate from the
mitotic division of single fertilized egg.
• Division of cell into daughter cells takes place
through cell cycle under controlled way.
• Cell cycle is the cyclic series of steps controlled
by specific set of genes and genes products in
order to reduce chances of error during
division cycle.These are called “Cell Divison
Cycle genes” or cdc genes.
Phases of cell cycle
• It consists of 2 major phases:
– Inter phase :
• G1 (pre-synthetic phase) : longest.
• S (DNA synthesis) :long.
• G2 (pre-mitotic phase): shorter.
– Cell division (mitotic phase) : shortest
Forces controlling cell cycle
• Who told the cell that”let’s start division”?
• Obviously “Molecular signals” in the form of
gene expression would tell the cell to jump
from one phase to next.
• But if DNA is mutated,damage or injuried
checkpoints would never let the cell enter in S
phase from G 1 phase untill repair does not
occur.If no repair cell would commit suicide.
• Originality of DNA is checked at checkpoints.
• G1-S Checkpoint:Only repaired DNA can pass
through this checkpoint and can enter into S
Phase otherwise get arrested.
• G2-M Checkpoint: G2 checkpoint would ensure
any error during DNA replication in S phase.If any
chromosomal part is missing,cell would be
arrested for repair.
• M Checkpoint: allignment of chromosome is
checked.Anaphase chromosome checking.
Positive & Negative affects of gene
expression during G 1 Phase
• Some group of genes activate other genes
group and they have positive coordinated
function.e.g. Genes products activating DNA
replication.While some inhibit these genes
expression as those cells in G 0.
• It means DNA replication inhibiting
genes(brakes) are over working and DNA
replication activating genes(acceleraters) are
How +ve affect is produced during
• Genes products produced by diploid cell:
• One group of genes produce proteins which
move out of cell called Growth Factors.
• Second group produce product which is inserted
into membrane of the same cell called Receptors
• Third group of genes would form product which
send signals to nucleus from receptor called
Signal Transducer proteins.
• STP would activate Responder proteins which
form transcriptional factor.
• TF act on special genes and form specific
molecules called Cycline.It is activated only
when cell has to do replication.But Cyclin-
Dependent Kinase(CDKs) remain always in cell
but inactive which work only in the presence
• Now cyclin would make complex with CDKs.And
become enzymatically active.
• This complex would phosphorylate Retinoblastema
Proteins (Rb) which has “Molecular Key(E2F)”.After
phosphorylation this key would be release and bind
with genes which move the cell to S Phase for
• Diifferent GF form dimer and send same signals to RB
to form TF.
• All above mentioned genes are called
“Protoncogenes”. Defects in theses genes cause cancer.
G0 phase :
It is the resting phase.
In these cells cyclin D is in decreased
Rb protein is in hypo-phosphorylated it means
less phosphoryation (active form).
Hence, holds the cell cycle at check point 1 by
inhibiting the expression of several
transcription proteins(E2F) that codes cyclins A
and E necessary for cycle progression.
Growth factor stimulation takes the G0 cells to
S phase :
Cyclin E/cdk and cyclin A/cdk regulate the
processes in phase S.
By phosphorylating and activating proteins
and enzymes that are involved in DNA
G2 check point :
located at the end of G2 phase trigerring onset mitosis after
ensuring cell Is ready for mitosis. The entry into mitosis is
initiated by Maturtion promoting factor (MPF).which contans
cdc25 an activting phosphatase which removes inhibitory
phosphates within the complex to facilitates transition to the
Cdc25 is inactivated in case of syntheis of faulty gene during
M phase (mitosis):
Mitosis is the distribution of the two sets of
chromosomes into two separate and equal nuclei.
It consists of four stages
• After M Phase Cytokinesis takes place and
parent cell divide into 2 daughter cells.
Positive regulators :
• Are those which control the changes
necessary for cell cycle to continue &
determine a cell's progress through the cell
cycle. They are pro mitotic.
• They include:-
– Cyclin-dependent kinases(cdks)
Different cyclin-CDK combinations determine the downstream
proteins targeted .
Cyclin A activtes cdk 1&2 ,
cyclin B activates cdk1,
cyclin D activates cdk4 & 6,(Phosphorylate RB proteins)
cyclin E activates cdk2. (Push cell from G1 To S Phase)
there are abt 8 different cyclins.
• These oppose the positive regultors i.e they
are anti mitotic.
• An optimum balance between the two
ensures a normal cell cycle.
• Over expression of positive regulators results
in unchecked cell division(cancer).ATP no
coversion to ADP.
• Over expression of negative regulators results
in cessation of cell division.
Different types of Negative
–Rb ( Retinoblastoma)proteins.
Rb (retinoblastoma) proteins :which bind to
transcription factor & inhibit syntheis of vital
proteins required for cell cycle.
Rb proteins act at G1 - S (pre-synthetic phase) .
Rb proteins get inactivated upon phosporylation
(cyclin-cdk dimer) &are active in the un
P53 gene ( guardian of genome) :codes for P53
protein whose conc in normal cells is very low but
increases upon DNA damage.