MUTATIONS IN P53 AND HOW THEY AFFECT ITS ROLE IN THE CELL CYCLE
P53 plays a very important role in controlling the cell cycle. Defective p53 can cause multiplication of abnormal cells, which leads to cancer. Over 50% of human tumours contain p53 mutants. Damaged DNA and some stress signals can activate the increase of p53 proteins while normally; the p53 protein level is available in lower quantities. To reduce the damaged DNA, p53 can repair DNA; it can perform growth arrest and initiate apoptosis (cell death).
Description of p53 p53, which is also known as TP53 or a tumour protein, has its locus on the chromosome 17p13.1 and codes for a protein. The p53 protein is responsible for tumour suppression: it stops the formation or growth of cancerous …show more content…
However, it is more likely for p53 to be aimed for mutations, resulting in tumours that are cancerous since greater than 50% of the mutations originate from the locus of 17p13.1 chromosome.
Functions of p53
Growth arrest stops the progress of the cell cycle when a damaged DNA is detected; this prevents the damaged DNA to be replicated throughout the cycle. p53 will activate protein transcription for the proteins involved in DNA repair to fix the damaged DNA detected in growth arrest by activating p53R2 which is its transcriptional target gene that codes for reductase which is important for DNA repair.
Apoptosis will be initiated by p53 when the DNA damage cannot be repaired further. Before the S-phase of the cell cycle, if cell is damaged, it will inhibit the activity of Cdk2 thus stopping the cell cycle until the damage is repaired. The cell will self-destruct by apoptosis if it is damaged …show more content…
The mutant p53 shows a gain-of-function effect over the wild type which includes cancer therapies and tumour prognosis. In about half of all human cancers, p53 is either lost or mutated and as a result, it gains or loses its functions as compared to the wild-type p53. However, the mutant p53 can be an advantage in the human body when it is used in cancer therapies and tumour prognosis. It could be a disadvantage when the cell proliferates. The cell divides uncontrollably as a result of the absence of MDM-2
Types of mutations that occur in p53
Mutations that can be found in the p53 protein can be determined by the structure of the protein or by the interaction of the protein with DNA. Type 1 mutations are missense mutations that affect the residue of the DNA binding surface and distort the protein-DNA contact points. Type 2 mutations are missense mutations that distort the protein conformation and type 3 mutations completely destroy the functionality of the protein [insertions/deletions (frame shift mutations), nonsense mutations, and splicing junction mutations] (Cho Y., 1994)
Mutation in p53 and the cell