• 主题
高级搜索  >
历史搜索 清空历史
首页> 外文学位 >Dissecting the molecular mechanisms of chromosome condensation and spindle assembly using Xenopus egg extracts.
【24h】

Dissecting the molecular mechanisms of chromosome condensation and spindle assembly using Xenopus egg extracts.

机译：用爪蟾卵提取物剖析染色体浓缩和纺锤体组装的分子机制。

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

Spindle assembly and chromosome condensation are essential mitotic processes that have evolved to ensure the faithful segregation of the genome during cell division. In order to fully understand these complex events, the functional contribution of individual cellular factors to spindle assembly and chromosome condensation must be defined. While significant progress has been made in these fields, much remains to be discovered. The goal of my research was to utilize Xenopus egg extracts to further characterize spindle assembly and chromosome condensation at the molecular and mechanistic levels.; In my first project, I investigated the role of the Regulator of Chromosome Condensation (RCC1) in mitotic chromosome condensation. RCC1 is an abundant chromatin-associated protein that binds directly to core histories. Additionally, as the guanine nucleotide exchange factor (GEF) for the small GTPase Ran, RCC1 generates a gradient of RanGTP around mitotic chromatin that locally activates spindle regulators. We hypothesized that RCCI could regulate chromosome condensation at either a structural level or via spatial regulation of condensation factors by the RanGTP gradient. While RCCI and a RanGTP gradient were found to be essential for nuclear assembly in interphase they were not required for chromatin condensation in metaphase extracts.; I next set out to identify and characterize microtubule-associated proteins (MAPs) that could be regulated by RanGTP during mitotic spindle assembly. A number of MAPs that contribute to spindle assembly are locally released from import receptors and activated around mitotic chromatin by a gradient of RanGTP. Xenopus nuclear factor 7 (Xnf7) was identified from X. laevis egg extracts as a mitotic MAP that binds to the importin alpha/beta complex.; I then returned to the topic of mitotic chromosome condensation when we set out to address the contribution of embryonic linker histone H1 to mitotic chromosomal architecture. Immunodepletion of histone H1 caused assembly of aberrant elongated chromosomes that extended off the metaphase plate and outside the perimeter of the spindle. Although functional kinetochores assembled, aligned and exhibited poleward movement, long and tangled chromosomes could not be segregated in anaphase.; My final graduate project focused on pioneering the use of Xenopus tropicalis egg extracts for in vitro assays, biochemistry and studying mechanisms that govern spindle length. These extracts support an array of functional assays commonly used in X. laevis extracts. (Abstract shortened by UMI.)
机译：纺锤体组装和染色体浓缩是必不可少的有丝分裂过程，已经进化以确保细胞分裂过程中基因组的忠实分离。为了充分理解这些复杂事件，必须定义单个细胞因子对纺锤体组装和染色体浓缩的功能贡献。尽管在这些领域已经取得了重大进展，但仍有许多地方有待发现。我的研究目标是利用非洲爪蟾卵提取物在分子和机制水平上进一步表征纺锤体装配和染色体浓缩。在我的第一个项目中，我研究了染色体浓缩调节剂（RCC1）在有丝分裂染色体浓缩中的作用。 RCC1是大量与染色质相关的蛋白，可直接与核心历史结合。此外，作为小GTPase Ran的鸟嘌呤核苷酸交换因子（GEF），RCC1在有丝分裂染色质周围产生RanGTP梯度，从而局部激活纺锤体调节因子。我们假设RCCI可以在结构水平或通过RanGTP梯度通过缩合因子的空间调节来调节染色体缩合。虽然发现RCCI和RanGTP梯度对于相间核组装至关重要，但它们对于中期提取物中的染色质浓缩并不需要。接下来，我着手鉴定和表征在有丝分裂纺锤体组装过程中受RanGTP调控的微管相关蛋白（MAPs）。许多有助于纺锤体组装的MAP从输入受体局部释放，并通过RanGTP梯度在有丝分裂染色质周围被激活。从X. laevis卵提取物中鉴定出非洲爪蟾核因子7（Xnf7）是一种有丝分裂的MAP，与导入蛋白α/β复合物结合。然后，当我们着手解决胚胎接头组蛋白H1对有丝分裂染色体结构的贡献时，我回到有丝分裂染色体浓缩的主题。组蛋白H1的免疫不全引起异常细长染色体的装配，该染色体延伸出中期板并延伸到纺锤体的外围。尽管功能性动植物装配，排列并表现出极向运动，但长而纠结的染色体不能在后期分离。我的最后一个研究生项目专注于开拓热带非洲爪蟾卵提取物用于体外测定，生物化学和研究控制纺锤长度的机制的应用。这些提取物支持X. laevis提取物中常用的一系列功能测定。 （摘要由UMI缩短。）

著录项

  • 作者

    Maresca, Thomas Joseph.;

  • 作者单位

    University of California, Berkeley.;

  • 授予单位 University of California, Berkeley.;
  • 学科 Biology Cell.
  • 学位 Ph.D.
  • 年度 2005
  • 页码 184 p.
  • 总页数 184
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 细胞生物学;
  • 关键词

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