Which of the following is known as the "guardian of the genome" -

p53; Guardian of genome p53 is a tumor suppressor gene. p53 gene is located on chromosome 17. p53 acts as molecular policeman that prevents the propagation of genetically damage cell. p53 gene product, i.e. p53 protein is a DNA binding protein in the nucleus, when called into action, it controls the transcription of several other genes. The ma 'or functional activities of the 53 rotein are cell c cle arrest and initiation of a o v.tosis in res onse to DNA damage. When there is DNA damage due to irradiation, UV light or mutagenic chemicals, there is rapid increase in p53 levels. p53 causes - Cell cycle arrest p-53 induces transcription of p21, a CDK inhibitor. p21 inhibit cyclin D-CDK-4 complex and there is arrest of cell cycle late in G1 phase. This allows time for DNA repair. DNA repair p-53 also helps in DNA repair directly by inducing transcription of GADD 45 (growth arrest and DNA damage). GADD 45 encodes a protein that is involved in DNA repair. If DNA damage is repaired successfully, p53 activate MDM-3 and this MDM-3 induce degradation of p-53 → Relieve in cell cycle block. If DNA damage cannot be successfully repaired, p53 induces apoptosis by inducing the activation of apoptosis-inducing gene BAX. So p53 prevents replication of cell with defective DNA → p53 functions as a critical gatekeeper against the formation of cancer. Mutation in p53 leads to carcinogenesis because of loss of the above protective mechanism. p-53 is the most common target for genetic alteration in human tumors: A little over 50% of human tumors contain mutation in this gene. (Note - Amongst oncogene RAS is involved most commonly).