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首页> 外文期刊>Molecular and Cellular Biology >Ku86 defines the genetic defect and restores X-ray resistance and V(D)J recombination to complementation group 5 hamster cell mutants.
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Ku86 defines the genetic defect and restores X-ray resistance and V(D)J recombination to complementation group 5 hamster cell mutants.

机译：Ku86定义了遗传缺陷，并恢复了X射线耐药性和V（D）J重组至互补组5仓鼠细胞突变体。

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摘要

X-ray-sensitive hamster cells in complementation groups 4, 5, 6, and 7 are impaired for both double-strand break repair and V(D)J recombination. Here we show that in two mutant cell lines (XR-V15B and XR-V9B) from group 5, the genetic defects are in the gene encoding the 86-kDa subunit of the Ku autoantigen, a nuclear protein that binds to the double-stranded DNA ends. These mutants express Ku86 mRNA containing deletions of 138 and 252 bp, respectively, and the encoded proteins contain internal, in-frame deletions of 46 and 84 amino acids. Two X-ray-resistant revertants of XR-V15B expressed two Ku86 transcripts, one with and one without the deletion, suggesting that reversion occurred by activation of a silent wild-type allele. Transfection of full-length cDNA encoding hamster Ku86 into XR-V15B cells resulted in a complete rescue of DNA-end-binding (DEB) activity and Ku70 levels, suggesting that Ku86 stabilizes the Ku70 polypeptide. In addition, cells expressing wild-type levels of DEB activity were fully rescued for X-ray resistance and V(D)J recombination, whereas cells expressing lower levels of DEB activity were only partially rescued. Thus, Ku is an essential component of the pathway(s) utilized for the resolution of DNA double-strand breaks induced by either X rays or V(D)J recombination, and mutations in the Ku86 gene are responsible for the phenotype of group 5 cells.
机译：互补组4、5、6和7中对X射线敏感的仓鼠细胞的双链断裂修复和V（D）J重组均受损。在这里，我们显示在第5组的两个突变细胞系（XR-V15B和XR-V9B）中，遗传缺陷存在于编码Ku自身抗原的86 kDa亚基的基因中，Ku自身抗原是一种与双链结合的核蛋白。 DNA末端。这些突变体表达分别含有138和252 bp缺失的Ku86 mRNA，并且编码的蛋白质含有46和84个氨基酸的内部框内缺失。 XR-V15B的两个X射线抗性回复体表达了两个Ku86转录本，一个有缺失，一个没有缺失，表明该回复是通过沉默的野生型等位基因的激活而发生的。将编码仓鼠Ku86的全长cDNA转染到XR-V15B细胞中，可以完全拯救DNA末端结合（DEB）活性和Ku70水平，这表明Ku86可以稳定Ku70多肽。另外，完全拯救了表达野生型水平的DEB活性的细胞的X射线抗性和V（D）J重组，而表达更低水平的DEB活性的细胞仅被部分拯救。因此，Ku是用于解析X射线或V（D）J重组诱导的DNA双链断裂的途径的重要组成部分，Ku86基因的突变是造成第5组表型的原因。细胞。

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