Which of the following is known as the "guardian of the genome"?
Ans. is 'a' i.e., p53 p53 is a tumour suppressor gene.At the time of DNA injury following irradiation, its level increases and it acts to cause cell cycle arrest (GTS)This arrest in cell cycle allows sufficient time for the repair of the D.N.A., and if the D.N.A repair cannot occur successfully, it directs the cell for apoptosisMechanism of p53When DNA damage occurs, p53 level is increased and it also becomes activated.- p53 assists in DNA repair by two mechanisms It acts through p 21 to cause cell cycle arrest, at G/S check point This allows time for D.N.A repairMeanwhile it causes D.N.A. repair through GADD 45If successful D.N.A. repair cannot occur through the above 2 mechanisms, the cell is directed by p53 to undergo apoptosis through BAX geneThus- p53 has the ability to control apoptosis in response to DNA damage. In response to DNA damage it is phosphorylated by genes that sense the damage and are involved in D.N.A. repair. p53 assists in DNA repair by causing G1 arrest and inducing DNA repair genes. A cell with damaged DNA that cannot be repaired is directed by p53 to undergo apoptosis. In view of these activities p53 has been right fully called "guardian of the genome".With homozygous loss of p53, DNA damage undergoes unrepaired mutation, becomes fixed in dividing cells and the cells turns on to a one way street leading to malignant transformation.So p53 functions as a critical gatekeeper against the formation of cancer. So p53 acts as a molecular policeman that prevents propagation of genetically damaged cells.Also see Q no 75 of Nov 2004.
p53
Mdm2
pl4
ATM
Carcinogenesis