Cernunnos-XLF, a recently identified non-homologous end-joining factor required for the development of the immune system.
OBJECTIVE
The analysis of immune deficiency conditions in humans has recently allowed the identification of a novel factor, Cernunnos, involved in DNA repair and required during the development of the immune system. The present review will focus on the information and new questions provided by the discovery of Cernunnos.


RESULTS
The study of human immune deficiency conditions associated with defective DNA repair led to the recent identification of Cernunnos. Cernunnos is required for the ubiquitous DNA repair process mainly used in mammals, the non-homologous end-joining pathway. The analysis of Cernunnos defect conditions demonstrated the essential role of this novel factor during the development of the immune system. Cernunnos is homologous to the non-homologous end-joining factor, XRCC4, and is the genuine homologue of the yeast non-homologous end-joining factor, Nej1. These observations shed new light on the process underlying the last step of the non-homologous end-joining pathway, the DNA ends ligation.


CONCLUSIONS
The elucidation of the molecular bases of rare inherited immune deficiencies associated with DNA repair defects provide considerable insights into our understanding of fundamental mechanisms such as the non-homologous end-joining ubiquitous DNA repair pathway.
Revy
Patrick
P
INSERM, Hôpital Necker-Enfants Malades, U768 Unité Développement Normal et Pathologique du Système Immunitaire, Paris, F-75015 France.
Malivert
Laurent
L
de Villartay
Jean-Pierre
JP
D000818:Animals; D004260:DNA Repair / Q000502:physiology*; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007107:Immune System / Q000254:growth & development*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D017386:Sequence Homology, Amino Acid; D016511:Severe Combined Immunodeficiency / Q000235:genetics / Q000276:immunology
D004268:DNA-Binding Proteins; C441270:NEJ1 protein, S cerevisiae; C508551:NHEJ1 protein, human; D029701:Saccharomyces cerevisiae Proteins; D045643:DNA Repair Enzymes