The document discusses regulation of the cell cycle. It explains that the cell cycle is regulated through checkpoints and cyclin-dependent protein kinases (Cdks) and cyclins. There are three main checkpoints - at the ends of G1 and G2 phases, and during metaphase. These checkpoints ensure DNA integrity and replication, and proper chromosome attachment before progression to the next phase. Cdks drive progression when activated by binding with cyclins, which are synthesized and degraded throughout the cycle in response to cellular signals.

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K.IRRFANA BANU
I M.Sc (Biotechnology).,

2. Definition
 The cell cycle or cell division cycle series of events that
take place in a cell leading to its division and
duplication of its DNA to produce two daughter cells.
 REGULATION OF CELL CYCLE:
Control of the cell cycle is necessary for a
couple of reasons.
 First, if the cell cycle were not regulated, cells could
constantly undergo cell division.

3. Second, internal regulation of the cell cycle is
necessary to signal passage from one phase to the next
at appropriate times.
Cyclin-dependent protein kinases
(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.

4. As their name suggests, cyclin-dependent protein
kinases are dependent on cyclins, another class of
regulatory proteins.
Cyclins bind to Cdks, activating the Cdks to
phosphorylate other molecules.
 Cyclins:
Cyclins are named such because they undergo a
constant cycle of synthesis and degradation during cell
division.
When cyclins synthesized,they act as an activating
protein and bind to Cdks forming a cyclin-Cdk
complex.

5.  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 signalling exit
from a particular phase.
 There are two classes of cyclins:
 Mitotic cyclins.
 G1 cyclins.
G1 Cyclins:
G1 cyclins bind to Cdk proteins during G1. once
bound and activated, the Cdk signals the cell’s exit
from G1 and entry into S phase.

6.  When the cell reaches an appropriate size and the
cellular environment is correct for DNA replication,
the cyclins begin to degrade. G1 cyclin degradation
deactivates the Cdk and leads to entry into S phase.
Mitotic 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(MRF).

7. This complex acts as the signal for the G2 cell to enter
mitosis. Once the mitotic cyclin degrades, MRF is
inactivated and the cell exists mitosis by dividing and
re- entering G1.
 The cellular signals that (cell size, completion of DNA
replication, and cellular environment) provide the
signals that regulate the synthesis and degradation of
cyclins.
 INTERNAL CHECKPOINT DURING THE CELL
CYCLE:
It is essential that the daughter cells exact duplicates
of the parent cells.

9.  Mistakes in the duplication or distribution of the
chromosomes lead to mutations that may be passed
forward to every new cell produced from an abnormal
cell.
 To prevent a compromised cell from continuing to
divide, internal control mechanisms operate at three
main cell cycle These checkpoints occur near the end
of G1, at the G2/M transition, and during metaphase.
 The cell cycle is controlled at three checkpoints.
 The integrity of the DNA is assessed at the G1
checkpoint. Proper chromosome duplication is
assessed at the G2 checkpoint.

10. Attachment of each kinetochore to a spindle fiber is
assessed at the M checkpoint.
G1 Checkpoint:
The G1 checkpoint determines whether all
conditions are favourable for cell division to proceed.
The G1 checkpoint, also called the restriction
point, is a point at which the cell irreversibly commits
to the cell division process.
Externally influences, such as growth factors,
plays a large role in carrying the cell past the G1
checkpoint.

11.  A cell that does not meet all the requirements will
not progress to the S phase.
The cell can halt the cycle and attempt to remedy
the problematic condition, or the cell can advance into
G0 inactive phase and await further signals when
conditions improve.
 If the cell meets the requirements for the G1
checkpoint,the cell will enter S phase and begin DNA
replication.
This transition,as with all of the major checkpoint
transitions in the cell cycle, is signaled by cyclins and
cyclin dependent kinases(CDKs). Cyclins are cell-
signaling molecules that regulate the cell cycle

12. .
G2 Checkpoint:
The G2checkpoint bars entry into the mitotic phase if
certain conditions are not met .
As with the G1 checkpoint ,cell size and protein
reserves are assesed .However,the most important role
of the G2 checkpoint is to ensure that all of the
chromosomes have been accurately replicated without
mistakes or damage.
If the checkpoint mechanism detect problems with
the DNA ,the cell cycle is halted and the cell attempts
to either complete DNA replication or repair rhe
damaged DNA.

13. If the DNA has been correctly replicated,cyclin
dependent kinases(CDKs) signal the beginning of
mitotic cell division.
M Checkpoint:
The M checkpoint occurs near the end of the
metaphase stage of mitosis. The M checkpoint is also
known as the spindle checkpoint because it
determines all the Sister chromatids are correctly
attached to the spindle microtubules.