• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity
【24h】

p48 Activates a UV-Damaged-DNA Binding Factor and Is Defective in Xeroderma Pigmentosum Group E Cells That Lack Binding Activity

机译：p48激活紫外线损坏的DNA结合因子，并在缺乏结合活性的黑皮病E组干细胞中有缺陷。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A subset of xeroderma pigmentosum (XP) group E cells lack a factor that binds to DNA damaged by UV radiation. This factor can be purified to homogeneity as p125, a 125-kDa polypeptide. However, when cDNA encoding p125 is translated in vitro, only a small fraction binds to UV-damaged DNA, suggesting that a second factor is required for the activation of p125. We discovered that most hamster cell lines expressed inactive p125, which was activated in somatic cell hybrids containing human chromosome region 11p11.2-11cen. This region excludedp125 but included p48, which encodes a 48-kDa polypeptide known to copurify with p125 under some conditions. Expression of human p48 activated p125 binding in hamster cells and increased p125 binding in human cells. No such effects were observed from expression of p48 containing single amino acid substitutions from XP group E cells that lacked binding activity, demonstrating that the p48 gene is defective in those cells. Activation of p125 occurred by a “hit-and-run” mechanism, since the presence of p48 was not required for subsequent binding. Nevertheless, p48 was capable of forming a complex with p125 either bound to UV-damaged DNA or in free solution. It is notable that hamster cells fail to efficiently repair cyclobutane pyrimidine dimers in nontranscribed DNA and fail to express p48, which contains a WD motif with homology to proteins that reorganize chromatin. We propose that p48 plays a role in repairing lesions that would otherwise remain inaccessible in nontranscribed chromatin.
机译：色素干皮（XP）E组细胞的一个子集缺少与紫外线辐射损坏的DNA结合的因子。该因子可以纯化为同质性，与125 kDa多肽p125相同。但是，当体外翻译编码p125的cDNA时，只有一小部分与紫外线损伤的DNA结合，这表明激活p125所需的第二个因子。我们发现大多数仓鼠细胞系均表达失活的p125，p125在包含人类染色体区域11p11.2-11cen的体细胞杂种中被激活。该区域不包括 p125 ，但包括 p48 ，其编码已知在某些条件下可与p125共纯化的48 kDa多肽。人p48的表达激活了仓鼠细胞中的p125结合，并增强了人类细胞中p125的结合。从缺乏结合活性的XP E组细胞中含有单个氨基酸取代的p48的表达未观察到这种作用，表明p48基因在那些细胞中是有缺陷的。 p125的激活是通过“运行即运行”机制发生的，因为后续结合不需要p48的存在。然而，p48能够与p125形成复合物，该复合物可以结合到紫外线损伤的DNA或在游离溶液中。值得注意的是，仓鼠细胞无法有效修复非转录DNA中的环丁烷嘧啶二聚体，并且无法表达p48，p48包含与重组染色质的蛋白质具有同源性的WD基序。我们建议p48在修复病变中发挥作用，否则这些病变在非转录染色质中仍将无法获得。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号