Cernunnos interacts with the XRCC4 x DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1.
DNA double strand breaks are considered as the most harmful DNA lesions and are repaired by either homologous recombination or nonhomologous end joining (NHEJ). A new NHEJ factor, Cernunnos, has been identified, the defect of which leads to a severe immunodeficiency condition associated with microcephaly and other developmental defects in humans. This presentation is reminiscent to that of DNA-ligase IV deficiency and suggests a possible interplay between Cernunnos and the XRCC4 x DNA-ligase IV complex. We show here that Cernunnos physically interacts with the XRCC4 x DNA-ligase IV complex. Moreover, a combination of sensitive methods of sequence analysis revealed that Cernunnos can be associated with the XRCC4 family of proteins and that it corresponds to the genuine homolog of the yeast Nej1 protein. Altogether these results shed new lights on the last step, the DNA religation, of the NHEJ pathway.
Callebaut
Isabelle
I
Département de Biologie Structurale, Institut de Minéralogie et de Physique des Milieux Condensés, CNRS UMR7590, Universités Paris 6 et Paris 7, Paris, F-75005 France. IsabelleCallebaut@impmc.jussieu.fr
Malivert
Laurent
L
Fischer
Alain
A
Mornon
Jean-Paul
JP
Revy
Patrick
P
de Villartay
Jean-Pierre
JP
D000595:Amino Acid Sequence; D002460:Cell Line; D000072481:DNA Ligase ATP; D011088:DNA Ligases / Q000737:chemistry*; D004260:DNA Repair; D045643:DNA Repair Enzymes; D004268:DNA-Binding Proteins / Q000737:chemistry*; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011485:Protein Binding; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry*; D017386:Sequence Homology, Amino Acid
D004268:DNA-Binding Proteins; C000607891:DNL4 protein, S cerevisiae; C000607893:LIG4 protein, human; C441270:NEJ1 protein, S cerevisiae; C508551:NHEJ1 protein, human; D029701:Saccharomyces cerevisiae Proteins; C101467:XRCC4 protein, human; D011088:DNA Ligases; D045643:DNA Repair Enzymes; D000072481:DNA Ligase ATP