Non-homologous end joining

Definition

Non-homologous end joining (NHEJ) is a DNA repair mechanism that directly joins two broken ends of DNA without the need for homologous templates. This process is critical in maintaining genome stability, particularly in response to double-strand breaks caused by various factors, including ionizing radiation and certain chemicals. NHEJ can result in insertions or deletions at the break site, contributing to structural variations such as inversions and translocations.

5 Must Know Facts For Your Next Test

1. NHEJ is most active in the G1 phase of the cell cycle when homologous recombination is less likely to occur.
2. The process involves several key proteins, including Ku proteins that bind to DNA ends and DNA-PKcs, which help recruit other factors necessary for repair.
3. Although NHEJ is essential for repairing double-strand breaks, it can introduce mutations due to its error-prone nature, leading to genomic instability.
4. NHEJ can play a role in generating genetic diversity during immune responses by rearranging genes in immune cells.
5. In cancers, aberrant NHEJ can contribute to genomic alterations that drive tumorigenesis, often through the formation of translocations.

Review Questions

• How does non-homologous end joining differ from homologous recombination in DNA repair mechanisms?
  • Non-homologous end joining (NHEJ) differs from homologous recombination primarily in that NHEJ does not require a homologous template for repairing double-strand breaks. Instead, it directly joins broken DNA ends, which can lead to insertions or deletions at the site of repair. In contrast, homologous recombination uses a homologous sequence as a template, resulting in more accurate repairs. This difference is significant because NHEJ is more error-prone and can lead to structural variations such as translocations.
• What role does non-homologous end joining play in the formation of structural variations like inversions and translocations?
  • Non-homologous end joining plays a critical role in the formation of structural variations such as inversions and translocations by improperly rejoining broken DNA ends. When two non-homologous chromosomes experience double-strand breaks and are repaired via NHEJ, segments of DNA from different chromosomes may be joined together. This misrepair can result in inversions if the broken ends are rejoined in reverse orientation or translocations if segments from different chromosomes are fused together. These events can significantly impact gene function and contribute to various diseases.
• Evaluate the implications of non-homologous end joining's error-prone nature on cancer development and treatment strategies.
  • The error-prone nature of non-homologous end joining (NHEJ) has significant implications for cancer development because it can lead to genomic instability through unregulated mutations and structural variations such as translocations. These alterations can activate oncogenes or deactivate tumor suppressor genes, driving tumorigenesis. In terms of treatment strategies, targeting the components of NHEJ could enhance the efficacy of therapies like radiation or certain chemotherapeutics by preventing cancer cells from effectively repairing their DNA damage. However, this approach requires careful consideration due to the potential effects on normal cells also relying on NHEJ for maintaining genomic integrity.

Related terms

double-strand break: A type of DNA damage where both strands of the DNA helix are severed, requiring repair mechanisms like NHEJ.

homologous recombination: A repair pathway that uses a homologous sequence as a template to accurately repair double-strand breaks, contrasting with the more error-prone NHEJ.

structural variation: Refers to large-scale alterations in DNA structure, including deletions, duplications, inversions, and translocations that can impact gene function and expression.