Advanced Molecular Biology

S-Phase
Synthesis of DNA
S-Phase Synthesis of DNA
WHAT TO BE TAKEN CARE OF,
DURING CELL DIVISION
DNA replication— two
problems for the cell:
1- It must occur with
extreme ACCURACY to
minimize the risk of
mutations in the next cell
generation.

2- Every nucleotide in
the genome must be
COPIED ONCE, and only
once, to prevent the
damaging effects of gene
amplification
S-Phase Synthesis of DNA
THE CELL CYCLE
Interphase (90% of the
cycle)
G1 Phase – growth

S Phase – synthesis of
DNA
G2 Phase – preparation
for the cell division

Mitotic phase
Mitosis – cell division
Cytokinesis – cytoplasm
division
S-Phase Synthesis of DNA
S phase
S Phase (Synthesis Phase)
is an essential aspect of
cell cycle

During S phase a number

of events additional to
chromosome replication
take place.

Initiation and completion

of DNA replication
defines the beginning and
ending of S phase of the
cell cycle.
S-Phase Synthesis of DNA
DNA replication begins at
origins of replication,
which are scattered at
numerous locations in
every chromosome.

During S phase, DNA

replication is initiated at
these origins when a DNA
helicase unwinds the
double helix and DNA
replication enzymes are
loaded onto the two single-
stranded templates.
S-Phase Synthesis of DNA
INITIATION PHASE OF DNA REPLICATION
First step occurs in late
mitosis

Early G1 – inactive DNA

helicases and pre-replicative
complex or preRC
(licencing of replication
origins) is formed

Origin recognition complex

– ORC (a multiplayer
protein) binds to replication
origins throughout the cell
cycle.
S-Phase Synthesis of DNA
At the onset of S phase,
chromosome
duplication is triggered
by the activation of S-
Cdk (Cyclin dependent
kinase).

S-Cdk activates specific

initiator proteins by
phosphorylation, that
unwinds the DNA and
initiate its replication at
replication origins.
S-Phase Synthesis of DNA

Once replication
origin is activated,
S-Cdk also inhibits
proteins that are
required to allow
that origin to
initiate DNA
replication
AGAIN.
S-Phase Synthesis of DNA
 S-Phase Synthesis of DNA
Summary
1- Duplication of the chromosomes in S phase involves:
accurate replication of entire DNA molecule in each
chromosome
duplication of the chromatin proteins that associate with the
DNA and govern various aspects of chromosome function.

2- Chromosome duplication is triggered by the activation of S-

Cdk, which activates proteins that unwind the DNA and initiate
its replication at replication origins.

3- Once a replication origin is activated, S-Cdk also inhibits

proteins which allow that origin to initiate DNA replication again
S-Phase Synthesis of DNA

Each origin is fired

once and only once
in each S phase and
cannot be reused
until the next cell
cycle.