...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG-CTG trinucleotide repeat
【24h】

DNA tandem repeat instability in the Escherichia coli chromosome is stimulated by mismatch repair at an adjacent CAG-CTG trinucleotide repeat

机译：相邻染色体CAG-CTG三核苷酸重复序列的错配修复会刺激大肠杆菌染色体中的DNA串联重复序列不稳定性

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

Approximately half the human genome is composed of repetitive DNA sequences classified into microsatellites, minisatellites, tandem repeats, and dispersed repeats. These repetitive sequences have coevolved within the genome but little is known about their potential interactions. Trinucleotide repeats (TNRs) are a subclass of microsatellites that are implicated in human disease. Expansion of CAG-CTG TNRs is responsible for Huntington disease, myotonic dystrophy, and a number of spinocerebellar ataxias. In yeast DNA double-strand break (DSB) formation has been proposed to be associated with instability and chromosome fragility at these sites and replication fork reversal (RFR) to be involved either in promoting or in preventing instability. However, the molecular basis for chromosome fragility of repetitive DNA remains poorly understood. Here we show that a CAG-CTG TNR array stimulates instability at a 275-bp tandem repeat located 6.3 kb away on the Escherichia coli chromosome. Remarkably, this stimulation is independent of both DNA double-strand break repair (DSBR) and RFR but is dependent on a functional mismatch repair (MMR) system. Our results provide a demonstration, in a simple model system, that MMR at one type of repetitive DNA has the potential to influence the stability of another. Furthermore, the mechanism of this stimulation places a limit on the universality of DSBR or RFR models of instability and chromosome fragility at CAG-CTG TNR sequences. Instead, our data suggest that explanations of chromosome fragility should encompass the possibility of chromosome gaps formed during MMR.
机译：人类基因组的大约一半由重复的DNA序列组成，这些DNA分为微卫星，小卫星，串联重复和分散重复。这些重复序列在基因组内共同进化，但对其潜在相互作用知之甚少。三核苷酸重复序列（TNRs）是与人类疾病有关的微卫星亚类。 CAG-CTG TNRs的扩展与亨廷顿病，强直性营养不良和许多脊髓小脑共济失调有关。有人提出在酵母DNA中双链断裂（DSB）的形成与这些位点的不稳定性和染色体脆性有关，而复制叉逆转（RFR）则与促进或预防不稳定性有关。但是，关于重复DNA染色体易碎性的分子基础仍然知之甚少。在这里，我们显示了CAG-CTG TNR阵列会刺激位于大肠杆菌染色体上6.3 kb处的275 bp串联重复序列的不稳定性。值得注意的是，这种刺激既与DNA双链断裂修复（DSBR）和RFR无关，又取决于功能错配修复（MMR）系统。我们的结果在一个简单的模型系统中证明了一种重复DNA上的MMR有可能影响另一种重复DNA的稳定性。此外，这种刺激机制限制了CAG-CTG TNR序列的不稳定性和染色体脆性的DSBR或RFR模型的普遍性。相反，我们的数据表明，染色体易碎性的解释应涵盖在MMR期间形成染色体缺口的可能性。

著录项

  • 来源
  • 作者

    John K. Blackwood; Ewa A. Okely; Rabaab Zahra; John K. Eykelenboom; David R. F. Leach;

  • 作者单位

    Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JR, United Kingdom;

    Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JR, United Kingdom;

    Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JR, United Kingdom;

    Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JR, United Kingdom;

    Institute of Cell Biology, School of Biological Sciences, University of Edinburgh, Edinburgh, EH9 3JR, United Kingdom;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    dna repair; dna replication; fragile site;

    机译：dna维修DNA复制;脆弱的网站;

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