Nonhomologous end-joining factor 1
Rendering based on PDB 2QM4.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2QM4, 2R9A, 3Q4F, 3RWR, 3SR2, 3W03
Identifiers
Symbols	NHEJ1; XLF
External IDs	OMIM: 611290 MGI: 1922820 HomoloGene: 11714 GeneCards: NHEJ1 Gene
Gene Ontology Molecular function • DNA binding • protein binding Cellular component • nucleus • nonhomologous end joining complex Biological process • double-strand break repair via nonhomologous end joining • DNA recombination • central nervous system development • response to ionizing radiation • B cell differentiation • T cell differentiation • positive regulation of ligase activity Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	79840	75570
Ensembl	ENSG00000187736	ENSMUSG00000026162
UniProt	Q9H9Q4	Q3KNJ2
RefSeq (mRNA)	NM_024782	NM_029342
RefSeq (protein)	NP_079058	NP_083618
Location (UCSC)	Chr 2: 219.94 – 220.03 Mb	Chr 1: 74.97 – 75.05 Mb
PubMed search	[1]	[2]
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Non-homologous end-joining factor 1 (NHEJ1), also known as Cernunnos or XRCC4-like factor (XLF), is a protein that in humans is encoded by the NHEJ1 gene.^[1] XLF was originally discovered as the protein mutated in five patients with growth retardation, microcephaly, and immunodeficiency.^[2] The protein is required for the non-homologous end joining (NHEJ) pathway of DNA repair. Patients with XLF mutations also have immunodeficiency due to a defect in V(D)J recombination, which uses NHEJ to generate diversity in the antibody repertoire of the immune system. XLF interacts with DNA ligase IV and XRCC4 and is thought to be involved in the end-bridging or ligation steps of NHEJ. The yeast (Saccharomyces cerevisiae) homolog of XLF is Nej1.^[3]

Phenotypes [link]

In contrast to the profound immunodeficiency phenotype of XLF deletion in humans, deletion of XLF alone has a mild phenotype in mice.^[4] However, combining a deletion of XLF with deletion of the ATM kinase causes a synthetic defect in NHEJ, suggesting partial redundancy in the function of these two proteins in mice.^[5]

Structure [link]

XLF is structurally similar to XRCC4, existing as a constitutive dimer with an N-terminal globular head domain, an alpha-helical stalk, and an unstructured C-terminal region (CTR).^[6]

Interactions [link]

XLF has been shown to interact with XRCC4,^[7] and with Ku protein,^[8] and it can also interact weakly with DNA.^[9][10] Co-crystal structures of XLF and XRCC4 suggest that the two proteins can form hetero-oligomers via head-to-head interaction of alternating XLF and XRCC4 subunits.^[11][12][13] These XRCC4-XLF filaments have been proposed to bridge DNA prior to end ligation during NHEJ. Formation of XRCC4-XLF oligomers can be disrupted by interaction of the C-terminal domain of XRCC4 with the BRCT domain of DNA ligase IV.^[11]

References [link]

Further reading [link]

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