...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Current Biology: CB >BRCA1/BARD1 orthologs required for DNA repair in Caenorhabditis elegans
【24h】

BRCA1/BARD1 orthologs required for DNA repair in Caenorhabditis elegans

机译：秀丽隐杆线虫DNA修复所需的BRCA1 / BARD1直系同源物

获取原文
获取原文并翻译 | 示例
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

Inherited germline mutations in the tumor suppressor gene BRCA1 predispose individuals to early onset breast and ovarian cancer [1]. BRCA1 together with its structurally related partner BARD1 is required for homologous recombination and DNA double-strand break repair, but how they perform these functions remains elusive [2, 3]. As part of a comprehensive search for DNA repair genes in C. elegans, we identified a BARD1 ortholog. In protein interaction screens, Ce-BRD-1 was found to interact with components of the sumoylation pathway, the TACC domain protein TAC-1, and most importantly, a homolog of mammalian BRCA1. We show that animals depleted for either Ce-brc-1 or Ce-brd-1 display similar abnormalities, including a high incidence of males, elevated levels of p53-dependent germ cell death before and after irradiation, and impaired progeny survival and chromosome fragmentation after irradiation. Furthermore, depletion of ubc-9 and tac-1 leads to radiation sensitivity and a high incidence of males, respectively, potentially linking these genes to the C. elegans BRCA1 pathway. Our findings support a shared role for Ce-BRC-1 and Ce-BRD-1 in C. elegans DNA repair processes, and this role will permit studies of the BRCA1 pathway in an organism amenable to rapid genetic and biochemical analysis.
机译：肿瘤抑制基因BRCA1中遗传的种系突变使个体更容易罹患早期乳腺癌和卵巢癌[1]。同源重组和DNA双链断裂修复需要BRCA1及其与结构相关的伴侣BARD1，但是它们如何执行这些功能仍然不清楚[2，3]。作为对秀丽隐杆线虫DNA修复基因进行全面搜索的一部分，我们鉴定了一个BARD1直系同源物。在蛋白质相互作用筛选中，发现Ce-BRD-1与sumoylation途径的成分，TACC域蛋白TAC-1相互作用，最重要的是与哺乳动物BRCA1的同源物相互作用。我们显示，被消耗掉Ce-brc-1或Ce-brd-1的动物表现出相似的异常，包括雄性高发，辐射前后p53依赖的生殖细胞死亡水平升高以及子代存活和染色体断裂受损照射后。此外，ubc-9和tac-1的耗竭分别导致辐射敏感性和雄性高发，这可能将这些基因与秀丽隐杆线虫BRCA1途径联系起来。我们的发现支持Ce-BRC-1和Ce-BRD-1在秀丽隐杆线虫DNA修复过程中的共同作用，并且该作用将允许对适合快速遗传和生化分析的生物中BRCA1途径进行研究。

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