Non-homologous end joining (NHEJ)

Definition

Non-homologous end joining (NHEJ) is a critical DNA repair mechanism that directly joins two broken ends of DNA without the need for a homologous template. This process is vital for maintaining genomic stability, especially after DNA damage, which can occur from various sources, including plasma-induced factors. NHEJ operates throughout the cell cycle and is particularly active in the G1 phase when homologous recombination is not available.

5 Must Know Facts For Your Next Test

1. NHEJ is predominant in higher eukaryotes and operates efficiently even in the absence of a homologous template, making it essential for rapid repair.
2. The process involves several key proteins, including Ku70/80, DNA-PKcs, and ligase IV, which work together to recognize DNA breaks and seal them.
3. NHEJ can lead to insertions or deletions at the repair site, which may result in mutations, but it is often preferred for its speed over accuracy.
4. This repair pathway plays a significant role in V(D)J recombination, a process critical for the development of immune diversity.
5. NHEJ can be influenced by various factors such as cell cycle stage and the presence of reactive oxygen species, which can enhance plasma-induced DNA damage.

Review Questions

• How does non-homologous end joining (NHEJ) differ from homologous recombination in terms of its mechanisms and outcomes?
  • Non-homologous end joining (NHEJ) differs from homologous recombination primarily in its reliance on DNA templates. While NHEJ directly joins broken DNA ends without needing a homologous template, homologous recombination requires a similar or identical sequence to guide the repair. This distinction means that NHEJ is faster but less accurate, often resulting in small insertions or deletions at the break site. In contrast, homologous recombination provides precise repairs but is restricted to specific phases of the cell cycle when a homologous template is available.
• Discuss the role of Ku proteins in the non-homologous end joining process and how they contribute to DNA repair efficiency.
  • Ku proteins are crucial components of the NHEJ pathway as they bind to the broken ends of DNA, protecting them from degradation and stabilizing the repair process. Once bound, they recruit other essential proteins like DNA-PKcs and ligase IV to facilitate further processing and ligation of the ends. This assembly of repair machinery enables efficient and rapid DNA repair, making Ku proteins key players in maintaining genomic stability after plasma-induced damage or other stressors.
• Evaluate the implications of non-homologous end joining on genetic stability and its potential impact on cancer development when this pathway is dysregulated.
  • The implications of non-homologous end joining (NHEJ) on genetic stability are significant. While NHEJ allows for quick repair of double-strand breaks, its propensity to introduce mutations through insertions or deletions can lead to genomic instability. When NHEJ is dysregulated or overly active, as seen in some cancers, it may contribute to tumorigenesis by promoting chromosomal rearrangements or mutations that drive uncontrolled cell proliferation. Understanding these dynamics is essential for developing targeted cancer therapies that exploit weaknesses in the NHEJ pathway.

Related terms

DNA Damage Response:

A complex cellular network that detects and repairs DNA damage, ensuring genomic integrity and preventing mutations.

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

Ku Proteins: A family of proteins that play a crucial role in NHEJ by recognizing and binding to the broken DNA ends, facilitating their repair.