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首页> 外文学位 >Genetic interactions between a spindle pole body (SPB) gene kar1, and the PKC1 MAP kinase cascade and nuclear envelope proteins.
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Genetic interactions between a spindle pole body (SPB) gene kar1, and the PKC1 MAP kinase cascade and nuclear envelope proteins.

机译：纺锤极体（SPB）基因kar1与PKC1 MAP激酶级联和核被膜蛋白之间的遗传相互作用。

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摘要

The most important function of microtubule organizing centers (MTOCs) is to establish the mitotic spindle, the machinery by which chromosomes segregate during cell division. For spindle formation, the MTOC duplicates to establish the two spindle poles. The yeast MTOC is a nuclear envelope embedded structure called the spindle pole body (SPB). My thesis work has identified two sets of interacting genes. One set encodes components of a signal transduction pathway that may be important for regulation of SPB duplication. Another set encodes nuclear envelope proteins that may be important in structural aspects of SPB assembly and its association with the nuclear envelope.; The kar1-Delta17 allele causes a temperature sensitive defect in SPB duplication due to failure to localize yeast centrin/Cdc31p to the SPB. As the core of my thesis work, I performed a synthetic lethal screen with a kar1-Delta17 strain to identify regulatory and structural SPB components that interact with Kar1p and/or Cdc31p. I identified mutations in three different genetic loci, REG1, MPK1, and NEM1, as being synthetically lethal with kar1-Delta17 and further characterized two of the genes, MPK1 and NEM1.; MPK1 is the MAP kinase of the PKC1 cell integrity pathway. Multiple PKC1 pathway components showed genetic interactions specifically with those SPB duplication mutants that interact with CDC31. We provide evidence that the genetic interactions were not due to cell integrity defects of the SPB duplication mutants but rather because PKC1 pathway promotes SPB duplication by acting on CDC31 or a functionally related gene. The study also showed a previously unreported link between SPC110 and CDC31 suggesting that CDC31 and SPC110 have interrelated functions in vivo.; Mutations in NEM1 and SPO7 encoding physically interacting nuclear envelope integral membrane proteins, showed genetic interactions specifically with kar1-Delta17 and not other SPB duplication mutants. Overexpression of NEM1 partially suppressed the temperature sensitive growth defect of kar1-Delta17 , indicating the two proteins had overlapping functions. Genetic analysis suggest that NEM1 is required for residual Kar1-Delta17p function in SPB duplication. To explain the genetic interactions, we propose that Nem1p, and possibly Spo7p, associate with Kar1p and assists in SPB duplication.
机译：微管组织中心（MTOC）的最重要功能是建立有丝分裂纺锤体，这是染色体在细胞分裂过程中分离的机制。对于主轴成形，MTOC复制以建立两个主轴极。酵母MTOC是一种被称为纺锤极体（SPB）的核膜包埋结构。我的论文确定了两组相互作用的基因。一组编码信号转导途径的成分可能对调节SPB复制很重要。另一组编码核包膜蛋白，这可能在SPB组装的结构方面及其与核包膜的结合中很重要。 kar1-Delta17等位基因导致SPB复制过程中出现温度敏感缺陷，原因是无法将酵母centrin / Cdc31p定位到SPB。作为我论文工作的核心，我用kar1-Delta17菌株进行了合成致死筛选，以鉴定与Kar1p和/或Cdc31p相互作用的调节性和结构性SPB成分。我确定了三个不同的基因位点REG1，MPK1和NEM1的突变，它们与kar1-Delta17合成致死，并进一步表征了两个基因MPK1和NEM1。 MPK1是PKC1细胞完整性途径的MAP激酶。多个PKC1途径组分显示出与那些与CDC31相互作用的SPB复制突变体特别地遗传相互作用。我们提供的证据表明遗传相互作用不是由于SPB复制突变体的细胞完整性缺陷，而是因为PKC1途径通过作用于CDC31或功能相关基因而促进SPB复制。该研究还显示了SPC110和CDC31之间以前未报道的联系，表明CDC31和SPC110在体内具有相互关联的功能。 NEM1和SPO7中的编码物理相互作用的核被膜整合膜蛋白的突变，显示出与kar1-Delta17特异性的遗传相互作用，而不与其他SPB复制突变体相互作用。 NEM1的过表达部分抑制了kar1-Delta17的温度敏感性生长缺陷，表明这两种蛋白具有重叠的功能。遗传分析表明，NEB1是SPB复制中残余Kar1-Delta17p功能所必需的。为了解释遗传相互作用，我们建议将Nem1p（可能还有Spo7p）与Kar1p结合并协助SPB复制。

著录项

  • 作者

    Khalfan, Waheeda A.;

  • 作者单位

    Princeton University.;

  • 授予单位 Princeton University.;
  • 学科 Biology Molecular.; Biology Cell.; Biology Genetics.
  • 学位 Ph.D.
  • 年度 2001
  • 页码 190 p.
  • 总页数 190
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 分子遗传学;细胞生物学;遗传学;
  • 关键词

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