Abstract:
From Birth to Rebirth, every living cell progress through a defined set of well regulated
events that constitute the “Cell Cycle”. This complex and well coordinated set of events with
an accurate and precise control in creating a copy of its own is referred to as the cell division
cycle. One of the most common means by which mammalian somatic cells divide is by
“Mitosis”. The Mitotic cell cycle comprises of totally five parts, two phases S and M, which
are the most active phase with two gap phases G1 and G2, separating these two phases and a
resting or quiescent phase called G0 phase. Proteins required for increasing the cell size and
replicating DNA are synthesised during G1 phase followed by S phase where the genomic
DNA is doubled. Following this phase ensues the second gap phase G2 where the cell
prepares itself before it is committed to the phase of segregation and division called as the
mitotic phase or M phase. During this phase the doubled genetic material condenses to form
chromosomes, which align over the equatorial region to finally get segregated into the two
identical daughter cells.
In order to ensure the faithful segregation of genetic material to the next generation the whole
process needs to be constantly monitored. Hence every entry and exit points in the various
phases of cell cycle are controlled by dedicated checkpoint machinery that exist within each
cell. These control mechanisms basically exist at two levels. Firstly, at the level of switching a resting cell i.e. G0 phase to G1 and subsequent phases of the cycle. This first layer of
control is affected generally by factors external to the cell. The second layer is an internal
quality control checkpoint system. In general there are three major checkpoints involved
during cell cycle, namely G1 checkpoint, G2 checkpoint and M phase checkpoint. These
checkpoints ensure correct transmission of genetic information during cell division by
constant surveillance for the appearance of any chromosomal aberrations and checking the
completeness of events that had occurred in the previous phase. Checkpoints take place
towards the end of each phase of mitosis and must be passed before signalling to proceed
further and enter into next stage. If errors are sensed during this, the rescue mechanisms try to
operate in correcting them and simultaneously try to arrest the cell growth and not progress
until repair. For example, a cell is normally prevented to progress from the G1 phase into S
phase if it has errors, or mutations, in its genome. The most common defects are the DNA
damage and defective spindle alignment which are sensed by the DNA damage checkpoint
proteins and the Spindle Assembly checkpoint proteins respectively. If the damage is sensed
as irreparable, the cell is directed towards apoptosis, or programmed cell death (Elledge, S.J.,
1996).