Non-homologous end joining

Definition

Non-homologous end joining (NHEJ) is a DNA repair mechanism that directly joins the broken ends of DNA without the need for a homologous template. This process is crucial for fixing double-strand breaks, which can occur due to various factors such as radiation or chemical exposure. NHEJ plays a significant role in genome editing techniques, allowing for targeted alterations in the DNA sequence by creating intentional breaks, followed by repair through this pathway.

5 Must Know Facts For Your Next Test

1. NHEJ is considered the primary repair pathway for double-strand breaks in non-dividing cells, making it critical for maintaining genomic stability.
2. The process of NHEJ is generally faster than homologous recombination, allowing cells to quickly respond to DNA damage.
3. While NHEJ is efficient, it is error-prone and can lead to insertions or deletions (indels) at the site of repair, which can affect gene function.
4. Components involved in NHEJ include Ku proteins, which bind to the DNA ends, and DNA-PKcs, which phosphorylates other proteins to facilitate the repair process.
5. NHEJ is a key mechanism exploited in various genome editing techniques to induce targeted mutations or insert genes into specific locations in the genome.

Review Questions

• How does non-homologous end joining differ from homologous recombination in the context of DNA repair mechanisms?
  • Non-homologous end joining (NHEJ) and homologous recombination are two distinct DNA repair mechanisms. NHEJ directly ligates broken DNA ends without needing a template, making it faster but more error-prone, often leading to insertions or deletions. In contrast, homologous recombination uses a homologous sequence as a template for precise repair, resulting in fewer errors but requiring that the cell be in a certain phase of the cell cycle when homologous sequences are available.
• Discuss the role of non-homologous end joining in genome editing techniques like CRISPR-Cas9.
  • In genome editing techniques such as CRISPR-Cas9, non-homologous end joining plays a vital role after double-strand breaks are induced in the target DNA. Once CRISPR-Cas9 creates these breaks, NHEJ can be harnessed to introduce mutations or insertions at the site of action. The efficiency of NHEJ allows researchers to achieve quick genetic modifications, although this comes with the risk of unpredictable changes due to its error-prone nature.
• Evaluate the implications of using non-homologous end joining for therapeutic genome editing in clinical settings.
  • Using non-homologous end joining for therapeutic genome editing has significant implications for clinical applications. On one hand, its rapid action allows for swift interventions in gene therapy; on the other hand, its error-prone nature poses risks for unintended consequences such as oncogene activation or loss of gene function. Therefore, while NHEJ offers a powerful tool for genetic modification, careful consideration of potential off-target effects and long-term outcomes is essential when applying this method in medical treatments.

Related terms

CRISPR-Cas9: A revolutionary genome editing tool that uses a guide RNA to target specific DNA sequences and create double-strand breaks, which can be repaired through NHEJ or homology-directed repair.

DNA Ligase: An enzyme that facilitates the joining of DNA strands together by catalyzing the formation of phosphodiester bonds, often used in the NHEJ process.

Homologous recombination: A precise DNA repair mechanism that uses a homologous sequence as a template for repairing double-strand breaks, contrasting with the more error-prone NHEJ.