Cernunnos interacts with the XRCC4•DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1
Cernunnos interacts with the XRCC4•DNA-ligase IV complex and is homologous to the yeast nonhomologous end-joining factor Nej1
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DOI：
10.1074/jbc.c500473200
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发表时间：
2006-05-19
影响因子：
4.8
通讯作者：
de Villartay, Jean-Pierre
中科院分区：
文献类型：
--
作者：
Callebaut, Isabelle;Malivert, Laurent;de Villartay, Jean-Pierre
DNA双链断裂被认为是最有害的DNA损伤，并且通过同源重组或非同源末端连接（NHEJ）来修复。已经鉴定了一种新的NHEJ因子Cernunnos，其缺陷导致与人类小头畸形和其他发育缺陷相关的严重免疫缺陷状况。这种介绍让人想起DNA连接酶IV缺乏，并表明Cernunnos和XRCC4中心点DNA连接酶IV复合物之间可能存在相互作用。我们在这里表明，Cernunnos物理上与XRCC4中心点DNA连接酶IV复合物相互作用。此外，敏感的序列分析方法的组合显示，Cernunnos可以与XRCC4蛋白家族相关，并且它对应于酵母Nej1蛋白的真正同源物。总之，这些结果揭示了NHEJ途径的最后一步，DNA重新连接。
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 center dot DNA-ligase IV complex. We show here that Cernunnos physically interacts with the XRCC4 center dot 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.