Non-homologous end-joining factor 1

Non-homologous end-joining factor 1 (NHEJ1), also known as Cernunnos or XLF (XRCC4-like factor), is a protein that in humans is encoded by the NHEJ1 gene. It plays a critical role in the non-homologous end joining (NHEJ) pathway of DNA repair, which is a major mechanism for repairing double-strand breaks (DSBs) in DNA. DSBs can be caused by a variety of factors including ionizing radiation, reactive oxygen species, and certain chemicals, as well as during the process of V(D)J recombination, a critical part of the development of the immune system.

Function

NHEJ1 is essential for the repair of double-strand breaks in DNA by non-homologous end joining. This process is crucial for maintaining the integrity of the genome and for preventing genomic instability, which can lead to cancer. NHEJ1 functions by interacting with other proteins in the NHEJ pathway, including Ku70/Ku80 heterodimer, DNA-PKcs (DNA-dependent protein kinase, catalytic subunit), XRCC4, and DNA ligase IV. These interactions facilitate the alignment and ligation of the broken DNA ends, effectively repairing the break without the need for a homologous template.

Clinical Significance

Mutations in the NHEJ1 gene have been associated with a variety of genetic disorders, including Severe Combined Immunodeficiency (SCID), which is characterized by a profound deficiency in both T-cell and B-cell immunity. Patients with NHEJ1 mutations may also exhibit microcephaly, growth retardation, and a predisposition to cancer, highlighting the importance of NHEJ1 in human health and disease.

Molecular Biology

The NHEJ1 gene is located on chromosome 2 in humans and encodes a protein of 299 amino acids. The NHEJ1 protein contains several key domains that are important for its function in DNA repair, including a head-to-head interaction motif that allows it to dimerize with XRCC4, and a C-terminal domain that is essential for its interaction with DNA ligase IV.

Research Directions

Research on NHEJ1 continues to uncover its roles beyond DNA repair. Recent studies suggest that NHEJ1 may also be involved in the regulation of telomere length and structure, as well as in the response to viral infections. Understanding the full range of NHEJ1's functions may provide new insights into the mechanisms of genome maintenance and the development of novel therapeutic strategies for treating diseases associated with NHEJ1 dysfunction.

See Also

• DNA repair
• Double-strand break repair
• V(D)J recombination
• Genomic instability
• Severe Combined Immunodeficiency