nonhomologous end joining complex

Definition

Target type: cellularcomponent

A protein complex that plays a role in DNA double-strand break repair via nonhomologous end joining. Such complexes typically contain a specialized DNA ligase (e.g. Lig4 in eukaryotes) and one or more proteins that bind to DNA ends. [GOC:mah, PMID:17072889, PMID:17938628]

The nonhomologous end joining (NHEJ) complex is a crucial DNA repair pathway that operates primarily in the nucleus, specifically within the nuclear matrix and chromatin. It is composed of a diverse array of proteins that collaborate to mend double-strand breaks (DSBs) in DNA, which are particularly hazardous lesions that can lead to genome instability and cell death if left unrepaired. The cellular component of NHEJ is complex and dynamic, undergoing extensive rearrangements during the repair process.

The core components of the NHEJ complex include:

* **KU70 and KU80**: These two proteins form a heterodimer known as the KU heterodimer. This dimer is responsible for recognizing and binding to the broken ends of DNA, acting as a scaffold that brings the two broken ends together. It serves as the initial point of contact for the NHEJ machinery.
* **DNA-PKcs**: This protein kinase is recruited to the broken DNA ends by the KU heterodimer. DNA-PKcs acts as a central coordinator, phosphorylating other NHEJ proteins to regulate their activity and promote the assembly of the repair complex.
* **Artemis**: This nuclease plays a critical role in processing the DNA ends. It removes any overhanging nucleotides and removes the 5'-phosphate groups at the ends, creating a blunt-ended structure suitable for ligation.
* **XLF and XRCC4**: These two proteins cooperate with DNA ligase IV to catalyze the final step of NHEJ, the joining of the processed DNA ends. They form a stable complex that interacts with DNA ligase IV, enhancing its activity and ensuring efficient ligation.
* **Ligase IV**: This enzyme is responsible for catalyzing the formation of a phosphodiester bond between the two DNA ends, permanently sealing the break.

In addition to these core components, several other proteins contribute to the efficiency and fidelity of NHEJ, including:

* **PAXX**: This protein interacts with DNA-PKcs and is involved in the recruitment of the DNA ligase IV complex.
* **MRE11**: This nuclease participates in early steps of NHEJ, potentially processing DNA ends and contributing to the removal of damaged nucleotides.
* **53BP1**: This protein is involved in the regulation of NHEJ, promoting the repair of DNA breaks by this pathway and inhibiting alternative repair pathways.
* **RIF1**: This protein interacts with 53BP1 and contributes to the regulation of NHEJ, influencing the choice of repair pathways.

The dynamic interplay of these proteins within the NHEJ complex ensures the efficient and accurate repair of DSBs. The location of these proteins within the nuclear matrix and chromatin, in close proximity to DNA, facilitates their rapid response to DNA damage and promotes the restoration of genomic integrity. The intricate regulation of NHEJ components through phosphorylation and interactions with other proteins guarantees a precisely controlled process that minimizes errors and prevents the accumulation of mutations.
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Proteins (1)

Compounds (46)