Non-homologous end joining

Definition

Non-homologous end joining (NHEJ) is a DNA repair mechanism that directly joins broken ends of DNA together without the need for a homologous template. This pathway is crucial in repairing double-strand breaks that can occur due to various factors, such as ionizing radiation or certain chemicals. Unlike homologous recombination, which requires a sister chromatid for accurate repair, NHEJ is often error-prone, which can lead to mutations or genomic instability.

5 Must Know Facts For Your Next Test

1. NHEJ is the predominant pathway for repairing double-strand breaks in non-dividing cells, like those in the human body.
2. The NHEJ process involves several key proteins, including Ku proteins that recognize the DNA ends and DNA-PKcs that facilitate the repair.
3. Unlike homologous recombination, NHEJ does not require a sister chromatid, making it faster but more error-prone.
4. NHEJ can result in insertions or deletions at the site of the break, which may lead to mutations and contribute to cancer development.
5. NHEJ is crucial during immune system development, particularly in generating diversity in antibodies through rearrangement of immunoglobulin genes.

Review Questions

• Compare and contrast non-homologous end joining with homologous recombination in terms of their mechanisms and outcomes.
  • Non-homologous end joining (NHEJ) and homologous recombination are both essential for repairing double-strand breaks, but they differ significantly in their mechanisms and outcomes. NHEJ directly joins the broken ends without a template, which can lead to errors like insertions or deletions at the break site. In contrast, homologous recombination uses a homologous sequence as a template, resulting in more accurate repairs. This distinction means that while NHEJ is faster and simpler, it is also more prone to mutations compared to the precise nature of homologous recombination.
• Discuss the role of proteins involved in non-homologous end joining and how they contribute to DNA repair.
  • Proteins play critical roles in non-homologous end joining (NHEJ) by orchestrating various steps of the repair process. Key proteins like Ku70/Ku80 bind to the DNA ends and protect them from degradation. The DNA-PKcs protein complex then facilitates alignment and processing of these ends. Additionally, DNA ligase seals the final gaps between the joined ends, completing the repair. The coordinated action of these proteins ensures that NHEJ effectively restores the integrity of the DNA despite its potential for introducing errors.
• Evaluate the implications of non-homologous end joining's error-prone nature on genetic stability and cancer development.
  • The error-prone nature of non-homologous end joining (NHEJ) has significant implications for genetic stability and cancer development. While NHEJ provides a rapid response to double-strand breaks, its tendency to introduce mutations—such as insertions or deletions—can disrupt gene function or regulatory elements within the genome. This increased mutagenesis can lead to genomic instability, which is a hallmark of cancer. Consequently, understanding NHEJ's mechanics and outcomes becomes crucial in elucidating how these mutations may contribute to tumorigenesis and influence cancer treatment strategies.

Related terms

Double-strand break: A type of DNA damage where both strands of the DNA helix are severed, posing a significant threat to genomic integrity.

Homologous recombination: A DNA repair process that uses a homologous sequence as a template to accurately repair double-strand breaks.

DNA ligase: An enzyme that facilitates the joining of two DNA strands by forming a phosphodiester bond, essential in the NHEJ repair process.