Malivert Laurent, Callebaut Isabelle, Rivera-Munoz Paola, Fischer Alain, Mornon Jean-Paul, Revy Patrick, de Villartay Jean-Pierre
INSERM U768, Malades, U768, Unité de Développement Normal et Pathologique du Système Immunitaire, Hopital Necker-Enfants Malades, 149, rue de Sevres, 75015 Paris, France.
Mol Cell Biol. 2009 Mar;29(5):1116-22. doi: 10.1128/MCB.01521-08. Epub 2008 Dec 22.
The core nonhomologous end-joining DNA repair pathway is composed of seven factors: Ku70, Ku80, DNA-PKcs, Artemis, XRCC4 (X4), DNA ligase IV (L4), and Cernunnos/XLF (Cernunnos). Although Cernunnos and X4 are structurally related and participate in the same complex together with L4, they have distinct functions during DNA repair. L4 relies on X4 but not on Cernunnos for its stability, and L4 is required for optimal interaction of Cernunnos with X4. We demonstrate here, using in vitro-generated Cernunnos mutants and a series of functional assays in vivo, that the C-terminal region of Cernunnos is dispensable for its activity during DNA repair.
核心的非同源末端连接DNA修复途径由七个因子组成:Ku70、Ku80、DNA-PKcs、Artemis、XRCC4(X4)、DNA连接酶IV(L4)和Cernunnos/XLF(Cernunnos)。尽管Cernunnos和X4在结构上相关,并且与L4一起参与同一复合物,但它们在DNA修复过程中具有不同的功能。L4的稳定性依赖于X4而非Cernunnos,并且Cernunnos与X4的最佳相互作用需要L4。我们在此使用体外生成的Cernunnos突变体和一系列体内功能测定证明,Cernunnos的C末端区域在DNA修复过程中对其活性而言是可有可无的。