Non-homologous end joining

Non-homologous End Joining

Diagram of the non-homologous end joining process.

Non-homologous end joining (NHEJ) is a pathway that repairs double-strand breaks (DSBs) in DNA. It is one of the two major pathways for repairing DSBs, the other being homologous recombination. NHEJ is considered a more error-prone repair mechanism compared to homologous recombination because it does not require a homologous template and can result in the loss or gain of nucleotides at the break site.

Mechanism

NHEJ involves several key steps and proteins that facilitate the repair of DNA double-strand breaks:

Recognition and Binding

The process begins with the recognition of the DSB by the Ku protein complex, which consists of Ku70 and Ku80 subunits. This complex binds to the DNA ends and protects them from degradation.

Processing of DNA Ends

Once bound, the DNA ends may require processing to make them compatible for ligation. This processing can involve the removal of damaged nucleotides or the addition of nucleotides to fill in gaps. Enzymes such as the Artemis endonuclease and the DNA polymerase _ and _ are involved in this step.

Ligation

The final step in NHEJ is the ligation of the DNA ends. This is carried out by the DNA ligase IV complex, which is recruited to the site by the XRCC4 protein. The ligase seals the DNA backbone, completing the repair process.

Importance in Cells

NHEJ is crucial for maintaining genomic stability, especially in non-dividing cells where homologous recombination is not possible. It is also important in the immune system for the generation of diversity in antibodies and T-cell receptors through a process known as V(D)J recombination.

Clinical Implications

Defects in NHEJ can lead to increased sensitivity to ionizing radiation and a predisposition to certain types of cancer. Understanding NHEJ is also important in the context of gene therapy and genome editing technologies, such as CRISPR-Cas9, where controlled induction of DSBs is used to introduce genetic changes.

Related Pages

• DNA repair
• Homologous recombination
• V(D)J recombination
• Ku protein
• DNA ligase