Saccharomyces cerevisiae C1D is implicated in both non-homologous DNA end joining and homologous recombination
Saccharomyces cerevisiae C1D is implicated in both non-homologous DNA end joining and homologous recombination
复制标题
DOI：
10.1046/j.1365-2958.2002.03224.x
复制
发表时间：
2002-11-01
影响因子：
3.6
通讯作者：
Yavuzer, U
中科院分区：
文献类型：
--
作者：
Erdemir, T;Bilican, B;Yavuzer, U
C1 D是一种γ-辐射诱导的核基质蛋白，其与DNA依赖性蛋白激酶（DNA-PK）相互作用并激活DNA依赖性蛋白激酶（DNA-PK），DNA-PK对于DNA双链断裂的修复和V（D）J重组是必需的。最近，研究表明C1 D也可以与TRAX相互作用，并阻止TRAX与翻译蛋白（一种已知结合DNA断点连接的因子）的结合，并且C1 D的过度表达可以诱导p53依赖性细胞凋亡。综上所述，这些发现表明，哺乳动物C1 D可能参与通过调节参与DNA修复和重组的蛋白质的活性来维持基因组的完整性。为了获得C1 D的生物学功能的直接证据，我们表明在不同物种之间是高度保守的，我们分析了酿酒酵母C1 D同源物。我们报告说，YC 1D基因的破坏结果在温度敏感性和yc 1d突变株表现出缺陷的非同源DNA末端连接（NHEJ）和准确的DNA修复。此外，使用一种新的质粒为基础的体内重组试验，我们表明，yc 1d突变株也有缺陷的同源重组。这些结果表明，YC 1D涉及同源重组和NHEJ途径，用于修复DNA双链断裂。
C1D is a gamma-irradiation inducible nuclear matrix protein that interacts with and activates the DNA-dependent protein kinase (DNA-PK) that is essential for the repair of the DNA double-strand breaks and V(D)J recombination. Recently, it was demonstrated that C1D can also interact with TRAX and prevent the association of TRAX with Translin, a factor known to bind DNA break-point junctions, and that over expression of C1D can induce p53-dependent apoptosis. Taken together, these findings suggest that mammalian C1D could be involved in maintenance of genome integrity by regulating the activity of proteins involved in DNA repair and recombination. To obtain direct evidence for the biological function of C1D that we show is highly conserved between diverse species, we have analysed the Saccharomyces cerevisiae C1D homologue. We report that the disruption of the YC1D gene results in a temperature sensitivity and that yc1d mutant strains exhibit defects in non-homologous DNA end joining (NHEJ) and accurate DNA repair. In addition, using a novel plasmid-based in vivo recombination assay, we show that yc1d mutant strains are also defective in homologous recombination. These results indicate that YC1D is implicated in both homologous recombination and NHEJ pathways for the repair of DNA double-strand breaks.