Non-homologous end joining (NHEJ)

Definition

Non-homologous end joining (NHEJ) is a cellular mechanism used to repair double-strand breaks in DNA by directly ligating the broken ends without the need for a homologous template. This process is crucial for maintaining genomic stability and is active throughout the cell cycle, particularly in the G1 phase when homologous recombination is not available. NHEJ can lead to insertions or deletions at the site of repair, making it a less accurate method compared to homologous recombination.

5 Must Know Facts For Your Next Test

1. NHEJ is considered the primary pathway for repairing double-strand breaks in mammalian cells, particularly during the G1 phase of the cell cycle.
2. The process involves several key proteins, including Ku proteins and DNA-dependent protein kinase (DNA-PK), which help stabilize and ligate the broken ends.
3. While NHEJ is essential for cell survival and maintaining genomic integrity, it can introduce mutations due to its error-prone nature, leading to insertions or deletions.
4. NHEJ is important in immune system development, particularly in generating diversity in immunoglobulin genes through V(D)J recombination.
5. Defects in NHEJ can lead to various diseases, including cancer, as the inability to properly repair DNA breaks can result in chromosomal instability.

Review Questions

• How does non-homologous end joining contribute to genomic stability despite its potential for introducing mutations?
  • Non-homologous end joining plays a critical role in maintaining genomic stability by providing a rapid repair mechanism for double-strand breaks. Although this method is error-prone and can result in mutations, its ability to quickly restore DNA integrity helps prevent the accumulation of harmful breaks that could lead to cell death. Thus, while NHEJ may introduce errors, its timely action ensures that cells can continue to function and divide.
• What are the key proteins involved in the non-homologous end joining process, and what roles do they play?
  • Key proteins involved in non-homologous end joining include Ku proteins, which bind to the DNA ends and protect them from degradation, and DNA-dependent protein kinase (DNA-PK), which phosphorylates various substrates to facilitate end processing and ligation. Additionally, other proteins like XRCC4 and Ligase IV help complete the repair by joining the ends together. Together, these proteins orchestrate the rapid response needed for effective DNA repair.
• Evaluate the implications of defective non-homologous end joining on disease development, particularly cancer.
  • Defective non-homologous end joining can have significant implications for disease development, especially cancer. When NHEJ is impaired, cells become unable to effectively repair double-strand breaks, leading to an accumulation of genomic instability characterized by chromosomal rearrangements and mutations. This instability can promote tumorigenesis as it allows for oncogenes activation or tumor suppressor gene inactivation. Understanding the role of NHEJ defects in cancer biology highlights potential targets for therapeutic intervention and emphasizes the importance of proper DNA repair mechanisms in maintaining cellular health.

Related terms

Double-Strand Break (DSB): A type of DNA damage where both strands of the DNA helix are severed, posing a significant threat to genomic integrity.

Homologous Recombination (HR): A precise DNA repair process that uses a homologous sequence as a template to accurately repair double-strand breaks.

Ku Protein: A protein that binds to the ends of DNA double-strand breaks and plays a critical role in initiating the non-homologous end joining repair process.