positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator

Definition

Target type: biologicalprocess

Any process that activates or increases the frequency, rate or extent of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator. [GOC:TermGenie, PMID:17719541]

The positive regulation of DNA damage response, signal transduction by p53 class mediator resulting in transcription of p21 class mediator, is a complex and tightly regulated cellular process that ensures proper cellular response to DNA damage. It involves a cascade of events, initiated by the detection of DNA damage and culminating in the transcriptional activation of genes involved in cell cycle arrest, DNA repair, or apoptosis. Here is a detailed description of the process:

1. **DNA Damage Detection:** Upon exposure to DNA damaging agents, various sensors within the cell detect the damage. These sensors include ATM (ataxia telangiectasia mutated), ATR (ATM and Rad3-related), and DNA-PKcs (DNA-dependent protein kinase catalytic subunit).
2. **Activation of p53:** Activated sensors trigger a signaling cascade leading to the activation of p53, a key tumor suppressor protein. Activation involves phosphorylation and acetylation of p53, which stabilizes the protein and allows it to act as a transcription factor.
3. **p53-Mediated Transcription:** Activated p53 binds to specific DNA sequences called p53 response elements (REs) located in the promoter regions of target genes.
4. **Transcriptional Activation of p21:** One of the primary target genes regulated by p53 is p21 (also known as CDKN1A), a cyclin-dependent kinase inhibitor. Transcriptional activation of p21 by p53 is crucial for cell cycle arrest.
5. **Cell Cycle Arrest:** p21 inhibits the activity of cyclin-dependent kinases (CDKs) that are essential for cell cycle progression. Inhibition of CDKs leads to cell cycle arrest at the G1/S checkpoint, providing time for DNA repair.
6. **DNA Repair:** During cell cycle arrest, DNA repair mechanisms are activated. These mechanisms include base excision repair (BER), nucleotide excision repair (NER), and homologous recombination repair (HRR).
7. **Apoptosis (If Necessary):** If DNA damage is too extensive to be repaired, p53 can also trigger programmed cell death (apoptosis) to eliminate the damaged cell and prevent the accumulation of mutations.

This process exemplifies the intricate network of molecular interactions involved in maintaining genomic integrity. The p53-mediated response to DNA damage plays a critical role in preventing uncontrolled cell proliferation and tumorigenesis. It is a crucial example of how cells safeguard their genetic material and ensure proper functioning.'
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Proteins (1)

Compounds (2)