PATHOLOGY

Detailed explanation-1: -p53 is involved in almost all nuclear DNA repair pathways including BER, NER, MMR, NHEJ and HR [32]. The transcription-independent functions play a prominent role as a facilitator of DNA repair by halting the cell cycle to allow time for the repair machineries to restore genome stability [25].

Detailed explanation-2: -Activation of p53 in response to DNA damage is associated with a rapid increase in its levels and with an increased ability of p53 to bind DNA and mediate transcriptional activation. This then leads to the activation of a number of genes whose products trigger cell-cycle arrest, apoptosis, or DNA repair.

Detailed explanation-3: -In response to various cellular stress, P53 can activate the transcriptional upregulation of CDKN1A, which encodes for cell cycle inhibitor P21 [30]. P53 can also activate other genes like GADD45A, which also contributes to cell cycle arrest [31]. Following DNA damage, a myriad of DNA-protein activation occurs.

Detailed explanation-4: -In the cell, p53 protein binds DNA, which in turn stimulates another gene to produce a protein called p21 that interacts with a cell division-stimulating protein (cdk2).

Detailed explanation-5: -RETRA activates a number of p53-regulated genes and suppresses the growth of tumor cells carrying mutant p53 [50]. The mechanism of action of RETRA involves release of p73 from its blocking complex with mutant p53 [50]. Interestingly, this agent does not affect normal cells.