Non-homologous end joining

Definition

Non-homologous end joining (NHEJ) is a DNA repair mechanism that directly ligates the ends of broken DNA molecules without the need for a homologous template. This process is crucial for repairing double-strand breaks (DSBs) in the DNA, which can arise from various forms of DNA damage, including radiation and reactive oxygen species. NHEJ is considered an error-prone repair pathway, often resulting in small insertions or deletions at the site of the break.

5 Must Know Facts For Your Next Test

1. NHEJ is the primary pathway for repairing double-strand breaks in mammalian cells, especially in non-dividing cells.
2. The process involves several key proteins, including Ku proteins and DNA-PKcs, which bind to the broken DNA ends and initiate repair.
3. NHEJ does not require a homologous template, making it faster but also more prone to errors compared to homologous recombination.
4. This repair mechanism plays a vital role in maintaining genome integrity, particularly during immune cell development and responses.
5. Deficiencies in NHEJ can lead to increased susceptibility to cancer and other genetic disorders due to the accumulation of unrepaired DNA breaks.

Review Questions

• How does non-homologous end joining differ from homologous recombination in terms of accuracy and mechanism?
  • Non-homologous end joining (NHEJ) differs significantly from homologous recombination in both accuracy and repair mechanism. NHEJ directly ligates broken DNA ends without a homologous template, making it faster but often resulting in insertions or deletions that can introduce mutations. In contrast, homologous recombination uses a homologous sequence as a template, allowing for precise repair with minimal alterations to the original sequence. This fundamental difference highlights NHEJ's role as a quick fix at the expense of fidelity.
• What are some 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 and DNA-dependent protein kinase catalytic subunit (DNA-PKcs). Ku proteins bind to the free ends of broken DNA, protecting them and facilitating their alignment for ligation. DNA-PKcs then associates with the Ku complex to form a larger protein complex that activates further steps in the NHEJ process. These proteins ensure that the broken ends are efficiently processed and joined together, highlighting their crucial roles in maintaining genomic integrity.
• Evaluate the implications of non-homologous end joining deficiencies on human health, particularly regarding cancer development.
  • Deficiencies in non-homologous end joining can have significant implications for human health, particularly concerning cancer development. When this repair pathway fails to function properly, double-strand breaks may go unrepaired or be repaired inaccurately, leading to genomic instability. This instability can result in mutations that contribute to tumorigenesis. Moreover, certain genetic disorders linked to NHEJ deficiencies, such as severe combined immunodeficiency (SCID), illustrate how critical this repair mechanism is for both immune function and overall cellular health.

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 stability.

homologous recombination: A more accurate DNA repair mechanism that uses a homologous sequence as a template to repair double-strand breaks, resulting in fewer errors.

DNA ligase: An enzyme that facilitates the joining of DNA strands by catalyzing the formation of phosphodiester bonds, essential for completing the NHEJ process.