Non-homologous end joining

Definition

Non-homologous end joining (NHEJ) is a crucial DNA repair mechanism that directly joins broken ends of double-strand DNA breaks without the need for a homologous template. This pathway is vital in maintaining genomic stability, especially following radiation-induced damage that results in breaks in the DNA. By rapidly repairing these breaks, NHEJ plays a significant role in preventing mutations and chromosomal aberrations.

5 Must Know Facts For Your Next Test

1. NHEJ is the predominant repair pathway for double-strand breaks in non-dividing cells and operates throughout the cell cycle, although it is more active in the G1 phase.
2. This mechanism is relatively quick and efficient, allowing cells to respond promptly to DNA damage but may introduce errors, leading to mutations.
3. Proteins such as Ku70/80 and DNA-PKcs are essential for recognizing DNA ends and facilitating the NHEJ process.
4. Failure to properly execute NHEJ can lead to severe consequences, including chromosomal instability and an increased risk of developing cancer.
5. While NHEJ is an essential repair mechanism, its error-prone nature can contribute to the formation of various types of chromosomal aberrations, complicating genomic integrity.

Review Questions

• How does non-homologous end joining differ from homologous recombination in terms of mechanisms and accuracy of DNA repair?
  • Non-homologous end joining (NHEJ) differs from homologous recombination primarily in its mechanism and accuracy. NHEJ directly ligates broken DNA ends without needing a homologous template, making it a faster but potentially error-prone process. In contrast, homologous recombination utilizes a sister chromatid as a template for accurate repair, which typically occurs during specific phases of the cell cycle. This distinction highlights the trade-off between speed and fidelity in DNA repair mechanisms.
• Discuss the role of non-homologous end joining in response to radiation-induced DNA damage and its implications for cellular radiosensitivity.
  • Non-homologous end joining plays a critical role in responding to radiation-induced DNA damage, particularly double-strand breaks caused by ionizing radiation. By repairing these breaks quickly, NHEJ helps maintain genomic stability and prevents cell death. However, its error-prone nature can lead to mutations and chromosomal aberrations, which may contribute to variations in radiosensitivity among different cell types. Understanding this balance is essential for assessing how cells respond to radiation exposure.
• Evaluate the long-term consequences of defective non-homologous end joining on genomic integrity and cancer development.
  • Defective non-homologous end joining can have severe long-term consequences on genomic integrity, leading to increased chromosomal instability and a higher likelihood of accumulating mutations. This instability can foster an environment conducive to tumorigenesis as cells acquire additional genetic alterations over time. In many cancers, defects in NHEJ-related genes are linked to poor prognosis and treatment resistance, illustrating how compromised DNA repair pathways can profoundly affect cancer development and progression.

Related terms

Double-strand break: A type of DNA damage where both strands of the DNA helix are severed, often resulting from ionizing radiation or certain chemical agents.

Homologous recombination: A DNA repair mechanism that uses a homologous sequence as a template to accurately repair double-strand breaks, typically occurring in the S and G2 phases of the cell cycle.

Chromosomal aberrations: Structural changes in chromosomes that can result from improper repair of DNA damage, leading to potential genetic disorders or cancer.