Checkpoints in cell cycle:
As we know cells usually divide when they have doubled their content by volume, but
actually the control of the process of cell division is very complex and occur
precisely. All the process or steps of cell division occurs in sequence and also the cell
know when to proceed and when to wait and stop cell division.
A continuous cell division before DNA replication is completed or when chromosome
or spindle fibers are damaged brings catastrophic consequences to cell or even
organism. Therefore, every aspects of a cell is checked by its internal mechanism
before proceeding to cell division.
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 cell cycle can be halted until conditions
are favorable.
Numerous stops occur during the cycle to assess whether the next step should proceed
or not and these stops are known as check point.
A complex protein called Maturation promoting factor (MPF) have a significant
role is cell maturation and mitotic division. It is also referred as mitosis promoting
factor.
MPF is composed of cyclin and cyclin dependent kinases, these two protein
molecules are activated when combined together and are responsible for cell cycle to
cross various checkpoints.
In the cell cycle, there are three check points that involves cyclin-dependent kinases
(cdks). Each cdk has its own specific cyclin that initiates either G1 phase, S phase, or
M phase of cell cycle. Other check points that do not involve cdks also occurs at
transition phases of cell cycles.
Checkpoints in cell cycle is very important because it helps to halt the process of cell
division if there is genetic damage, giving the cell to repair the damage before cell
division. If the damage cannot be repaired then cell undergoes apoptosis and again if
the check point mechanism is failed then cell become cancerous.
Various checkpoints in cell cycle:
i. G1 check point:
The G1 checkpoint determines whether all conditions are favorable for cell division to
proceed or not. Such as damage to DNA and other external factors of cells are evaluated at
this checkpoint. If the conditions are inadequate, the cell will not be allowed to continue to
the S phase.
G1 checkpoint is also known as the restriction point at which the cell irreversibly commits to
the cell division process. Cell set up certain requirements to be fulfilled by the cell to pass
the check points.
External factor such as growth factors play a vital role in carrying the cell past the
G1 checkpoint. The cell will only pass the checkpoint if it has an appropriate size and has
adequate energy reserves.
At this point, the cell also checks for DNA damage.
A cell that does not meet all the requirements will not progress to the S phase. Those cells
halt the cycle and attempt to correct the problematic condition, or the cell may undergoes
inactivation into G0 phase and await for further signals when conditions improve.
If a cell meets all the requirements for the G1 checkpoint, the cell will enter S phase and
begin DNA replication.
This G1 checkpoint involves signaled by cyclins and cyclin dependent kinases (CDKs).
ii. G2 check point:
The G2 checkpoint ensures all of the chromosomes have been accurately replicated and that
the replicated chromosome is not damaged before cell enters mitosis.
G2 checkpoint prevents the cell from entering into the mitotic phase if certain conditions are
not met.
If the checkpoint mechanisms detect problems with the DNA, the cell cycle is halted and the
cell attempts to either complete DNA replication or repair the damaged DNA.
If the DNA has been correctly replicated, cyclin dependent kinases (CDKs) signal the
beginning of mitotic cell division
iii. M check point:
The M checkpoint occurs at the end of the metaphase of mitosis.
M checkpoint determines whether all the sister chromatids are correctly attached to the
spindle fiber before the cell enters the irreversible anaphase stage.
M checkpoint is also known as the spindle checkpoint because it determines whether all the
sister chromatids are correctly attached to the spindle microtubules or not.
At the end stage of metaphase, spindle fiber arising from opposite pole of cell attached to
kinetochore of centromere of sister chromatid in equatorial plane. Then the cell enter into
anaphase which is characterized by separation of sister chromosome toward opposite pole.
Since anaphase is irreversible step in cell cycle, M phase check point is very crucial which
ensure proper attachment of spindle to sister chromatids.
M check point also involves signal from cyclin dependent kinases.
