Regulation of the Cell Cycle

After cell division the daughter cells follow ONE of several pathways:

• Cells that can divide again immediately.

• Other cells enter G-0 phase. Some of them are
quiescent for a time but then re-enter G1 phase.
• Some specialist cells, for example nerve cells, do
not divide again.
• Other cells can be triggered by activities such as
wound repair to enter G1 phase of the cell cycle to
divide as required.
 To know how cell cycle controls you should
know the followings:
1. Signal for cell division Cyclins, CDK,
growth factors,
oncogenes AND
Phosphatase.
2. Signal for cell to not divide P53, P21,
Tumor suppressor
genes, CDK inhibitors.
3. checkpoint
 Cell cycle control

A checkpoint is one of several points in the

eukaryotic cell cycle at which the progression of a
cell to the next stage in the cycle or can be halted
(stopped) until conditions are favourable.
There are three checkpoints during cell cycle:
1. G1/S checkpoint
2. G2/M checkpoint
3. M checkpoint (mitosis checkpoint)
M checkpoint
 .

1. G1 checkpoint
Checks for: cell size, Nutrients, Growth factor and DNA
damage.
G1 checkpoint
• Controlled by G1 Cdk-cyclin
• Many additional levels of phosphorylation, dephosphor-
ylation regulate.

2. G2 checkpoint
Checks for: Cell size, DNA integrity and DNA replication.
3. M checkpoint
• Checks for: Alignment (All of the chromosomes are lined
up at the metaphase).
• chromosome attachment to spindle fibres.
 Cell cycle control
• As a cell approaches the end of the G1 phase it is
controlled at a vital checkpoint, called G1/S, where
the cell determines whether or not to replicate its
DNA. At this checkpoint the cell is checked for
DNA damage to ensure that it has all the necessary
cellular machinery to allow for successful cell
division.
• As a result of this check, which involves the
interactions of various proteins. Cells with intact
DNA continue to S phase; cells with damaged DNA
that cannot be repaired are arrested and "commit
suicide" through apoptosis, or programmed cell
 Cell cycle control

• A second such checkpoint occurs at the G2 phase

following the synthesis of DNA in S phase but
before cell division in M phase.
• Cells use a complex set of enzymes called kinases to
control various steps in the cell cycle. Cyclin
Dependent Kinases, or CDKs, are a specific enzyme
family that use signals to switch on cell cycle
mechanisms.
• CDKs themselves are activated by forming
complexes with cyclins, another group of regulatory
proteins only present for short periods in the cell
cycle.
 Cell cycle control

• This process also includes mechanisms to ensure

errors are corrected, and if not, the cells commit
suicide (apoptosis).

• In cancer, as a result of genetic mutations, this

regulatory process fails, resulting in uncontrolled
cell proliferation.
We will discuss two main families of proteins involved in this process (cell cycle):

1. Cyclin-Dependent Kinase (Cdks)

• A Cdks is an enzyme that adds negatively charged
phosphate groups to other molecules in a process
called phosphorylation.

• Through phosphorylation, Cdks signal the cell that it is

ready to pass into the next stage of the cell cycle.

• As their name suggests, Cyclin-Dependent Protein

Kinases are dependent on cyclins, another class of
regulatory proteins. Cyclins bind to Cdks, activating
 2. Cyclins
• Cyclins are named such because they undergo a
constant cycle of synthesis and degradation during
cell division.
• When cyclins are synthesized, they act as an
activating protein and bind to Cdks forming a cyclin-
Cdk complex.
• This complex then acts as a signal to the cell to pass
to the next cell cycle phase.
• Eventually, the cyclin degrades, deactivating the Cdk,
thus signaling exit from a particular phase. There are
different classes of cyclins: G1-cyclins, G1-S-cyclins,
S-cyclins and M-cyclins.
 Mitotic Cyclins (M-cyclins)
• Mitotic cyclins accumulate gradually during G2.
• Once they reach a high enough concentration, they can
bind to Cdks. When mitotic cyclins bind to Cdks in G2,
the resulting complex is known as Mitosis-promoting
factor (MPF).
• This complex acts as the signal for the G2 cell to enter
mitosis.
• Once the mitotic cyclins degrade, MPF is inactivated and
the cell exits mitosis by dividing and re- entering G1.
• The cellular signals that we described earlier (cell size,
completion of DNA replication, and cellular
environment) provide the signals that regulate the
synthesis and degradation of cyclins