Cernunnos-XLF, a recently identified non-homologous end-joining factor required for the development of the immune system

Abstract

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. 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. 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.