Guardian of Our Genome - P53


To understand the brilliantly engineered strategies of the gene P53, we first need to consider the cell cycle in which the cell prepares checks and divides itself, to allow cell growth and repair. Interphase consisting of: G1, S Phase, and G2 (in addition to G1 and G2 checkpoints), followed by Mitosis which includes Prophase Metaphase Anaphase and Telophase, enables the cell to successfully divide and replicate.

Between the start of G1 and G1 checkpoint, S-Phase-and-G2 checkpoint, G2 checkpoint and Metaphase is a mechanism that enables the cell to move along the cell cycle. Consisting of CDK’s (Cyclin Dependent Kinase) and Cyclin (cyclin partners), CDK's are protein molecules – dependent on cyclin. When cyclin bonds to CDK forming a "cyclin -CDK complex", phosphorylation of the complex takes place allowing the cell to continual move throughout cycle.

P53; also referred to as the guardian of the genome is by far on the most important genes within our bodies. The gene found on the short strand of chromosome 17, encodes for a protein made up of 393 amino acids – P53 Protein, regulating the cell cycle; functioning as a tumour suppressor (TP53).  53 denoting the molecular Mass of the protein – 53 kilodalton. On most occasions, the protein occurs at low levels and is generally unstable –quickly degraded by the degradation action of MdM2 protein (a protein formed by the P53 gene acting as a transcriptional regulator).


When DNA is damaged within the cell cycle, it triggers the expression of P53 gene – regulating a higher-level production of P53 protein. The protein being a transcriptional regulator of many genes– causes the transcription of a gene knows as “WAF-1”. The WAF-1 mRNA transcription forms a protein known as “P21”.  P21 acts as a inhibitor to the cyclin- CDK complex’s, preventing the damaged DNA from be carried through interphase into meta phase  to be synthesised, hence stopping any unwanted growth of a mutated gene. Arrest of the Cell cycle at the G1 phase allows time for the DNA to be repaired. Once repaired, the MdM2 protein(formed by the transcription signals of the P53 transcriptional regulator) – binds to the P53 protein forming a complex known as “P53 MDM2 complex”. This causes the protein molecule to become  degraded into lower levels, allowing the cell to come out of "arrest" and continue cell division. If DNA cannot be repaired, P53 causes "permanent arrest" known as senescence (deterioration with age/ lose of a cells power of division and growth) or it activates Apoptosis(controlled death of the cells growth and development – cell suicide).  

From this we can see whenever there is a damage within the DNA, P53 acts upon it, preventing synthesis of any harmful mutation, acting as the guardian of our genome- in other words a tumour suppressor. 


Hope you have found this intriguing, by Universal Medicine Team (Mathew George)

Sources :
https://www.ncbi.nlm.nih.gov/books/NBK22268/
https://www.nhs.uk/news/pregnancy-and-child/cancer-treatment-holds-fertility-hopes/
http://www.nhs.uk/news/2012/01January/Pages/statins-may-fight-cancer-cells.aspx
https://www.youtube.com/watch?v=-3Di4OgAhmc
https://www.youtube.com/watch?v=C-Njz_iSvLI
https://www.youtube.com/watch?v=AGEu88ujn5w

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