DNA Damage Response

Definition

DNA damage response refers to the series of cellular processes that detect and repair damage to DNA, ensuring genomic stability and preventing mutations. This response is crucial for maintaining cellular integrity, as it activates pathways that identify DNA lesions, signal their presence, and initiate repair mechanisms. Effective DNA damage response not only protects individual cells but also plays a key role in the overall health of the organism.

5 Must Know Facts For Your Next Test

1. The DNA damage response involves multiple pathways, including direct repair, nucleotide excision repair, and homologous recombination, each tailored to specific types of DNA damage.
2. Key proteins involved in the DNA damage response include ATM (Ataxia Telangiectasia Mutated) and ATR (ATM and Rad3-related), which are crucial for signaling and initiating repair processes.
3. If the damage is irreparable, the DNA damage response can trigger apoptosis to prevent the proliferation of damaged cells, thereby protecting the organism from potential cancerous growth.
4. The efficiency of the DNA damage response decreases with age, contributing to an increase in mutations and age-related diseases.
5. Defects in DNA damage response pathways are linked to various diseases, including cancer, highlighting its importance in maintaining genomic integrity.

Review Questions

• How do different DNA repair pathways contribute to the overall DNA damage response in cells?
  • Different DNA repair pathways are specialized to address various types of DNA damage, thus enhancing the effectiveness of the DNA damage response. For instance, direct repair mechanisms can quickly reverse certain modifications like methylation, while nucleotide excision repair removes bulky lesions caused by environmental factors. Homologous recombination is essential for repairing double-strand breaks accurately. By coordinating these diverse pathways, cells ensure comprehensive protection against mutations and maintain genomic stability.
• Discuss the roles of ATM and ATR in the DNA damage response and how they interact with other proteins involved in repair mechanisms.
  • ATM and ATR are central players in the DNA damage response, acting as sensors that detect DNA lesions and initiate signaling cascades. Upon detecting damage, ATM phosphorylates key substrates that activate cell cycle checkpoints and recruit repair proteins. ATR similarly responds to single-stranded DNA or replication stress. Together with checkpoint kinases, they help regulate the cell cycle's progression and coordinate repair processes by ensuring that any damaged DNA is repaired before replication continues, thus preventing further genetic instability.
• Evaluate how defects in the DNA damage response can lead to cancer development and what implications this has for therapeutic strategies.
  • Defects in the DNA damage response can lead to an accumulation of mutations due to ineffective repair processes, significantly increasing cancer risk. For example, mutations in genes like BRCA1 or BRCA2 compromise homologous recombination repair, leading to breast and ovarian cancers. Understanding these defects has critical implications for therapeutic strategies; targeted therapies can be developed to exploit these weaknesses. For instance, PARP inhibitors specifically target cells deficient in homologous recombination repair, providing a promising avenue for treating certain types of cancers linked to defective DNA damage responses.

Related terms

DNA Repair: The set of mechanisms by which a cell identifies and corrects damage to its DNA molecules.

Apoptosis: A form of programmed cell death that can be triggered by excessive DNA damage, allowing the body to eliminate potentially harmful cells.

Checkpoint Kinases: Proteins that monitor the integrity of DNA during the cell cycle and can halt progression if damage is detected.