The Cell Cycle
The Cell Cycle
The Interphase
The interphase comprises three phases called G1, S, and G2. The first stage of the
interphase is called the Gap phase 1 (G1 phase). During the G1 phase, the cell is
active at the biochemical level. The cell is growing and accumulating the building
blocks of chromosomal DNA and the associated proteins as well as accumulating
sufficient energy reserves to complete the task of replicating each chromosome in the
nucleus.
In the Synthesis phase (S phase), DNA replication occurs leading to two identical
double-strands. Furthermore, the centrosome is duplicated and the duplicated
centrosome will then give rise to the mitotic spindle, the apparatus that orchestrates
the movement of chromosomes during mitosis.
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In the Gap 2 phase (G2 phase), the cell grows and replenishes its energy stores and
synthesizes proteins necessary for DNA repair. Some cell organelles are duplicated,
and the cytoskeleton is dismantled to provide resources for the mitotic phase.
While some cells are constantly dividing, some cell types are at rest. These cells may
exit G1 and enter a resting state called G0. In G0, a cell is performing its function
without actively preparing to divide. G0 is a permanent state for some cells, while
others may re-start division if they get the right signals.
Although cyclins are the main regulatory molecules that determine the forward
momentum of the cell cycle, several other mechanisms regulate the cell cycle. These
mechanisms block the progression of the cell cycle when a problem is detected until
it is resolved. The best understood negative regulatory molecules are retinoblastoma
protein (Rb), p53, and p21. These proteins (Rb, p53, and p21) act at the checkpoints.
p53 is a multi-functional protein that has a major impact on the cell’s commitment to
division; it acts when there is damaged DNA in cells that are undergoing the
preparatory processes during G1. If damaged DNA is detected, p53 halts the cell cycle
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and recruits enzymes to repair the DNA. If the DNA cannot be repaired, p53 can trigger
apoptosis (cell suicide) to prevent the duplication of damaged chromosomes. An
increase in p53 leads to the transcriptional activation of p21. Production of p21 leads
to the inhibition of cell cycle progression by binding to and inhibiting the activity of the
Cdk/cyclin complexes.
Cancer
Cancer is the result of uncontrolled cell division caused by a breakdown of the
mechanisms regulating the cell cycle. The loss of control begins with a change in the
DNA sequence of a gene that codes for one of the regulatory molecules. Faulty
instructions lead to a protein that does not function as it should. Any disruption of the
monitoring system can allow other mistakes to be passed on to the daughter cells.
Each successive cell division will give rise to daughter cells with even more
accumulated damage. Eventually, all checkpoints become nonfunctional, and rapidly
reproducing cells crowd out normal cells, resulting in tumorous growth. Tumours are
groups of abnormal cells that form lumps or growths. They can start in any one of the
cells in the body. Tumours grow and behave differently, depending on whether they
are cancerous (malignant), non-cancerous (benign).
Cell death
When cells die, they do so in two main ways: by apoptosis or necrosis. Apoptosis is
programmed cell death; the cell dies as part of its normal programme of development,
or it may be lacking in growth factors, or it may be instructed to die by cells of the
immune system, because it has become infected, pre-cancerous or old. Cell
undergoing apoptosis are removed by phagocytes within the tissue preventing
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inflammation of the affected body part. Apoptosis is known to be induced via two main
pathways (Intrinsic and Extrinsic). On the other hand, necrosis is an unregulated cell
death mechanism caused by lack of nutrients or infection. During necrosis, the dying
cells release their contents leading to inflammation.