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首页> 外文学位 >A high-throughput screen for novel genes involved in maintaining genome stability and the DNA damage response pathway in Saccharomyces cerevisiae.
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A high-throughput screen for novel genes involved in maintaining genome stability and the DNA damage response pathway in Saccharomyces cerevisiae.

机译：高通量筛选涉及酿酒酵母中维持基因组稳定性和DNA损伤反应途径的新基因。

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摘要

Oncogenesis is frequently accompanied by rampant genome instability, which fuels genetic heterogeneity and resistance to targeted cancer therapy. I have developed an approach that allows precise, quantitative measurement of genome instability in a high-throughput format in Saccharomyces cerevisiae. My approach takes advantage of the strongly DNA damage-inducible gene RNR3, in conjunction with the Reporter Synthetic Genetic Array methodology, to infer mutants exhibiting genome instability by assaying for increased Rnr3 abundance. We screen for genome instability across ~4200 non-essential mutant yeast alleles in untreated conditions and in the presence of the DNA damaging agent MMS. Our results provide broad insights into the cellular processes and pathways required for genome maintenance. Preliminary follow-up work suggests that several genes have bona fide roles in the maintenance of genome stability. In addition, I conducted both screens in their entirety on two, highly orthogonal fluorescence imaging platforms and compared their reproducibility and sensitivity.
机译：癌变通常伴随着猖genome的基因组不稳定，加剧了遗传异质性和对靶向癌症治疗的抵抗力。我已经开发出一种方法，可以在酿酒酵母中以高通量格式精确，定量地测量基因组的不稳定性。我的方法利用强DNA损伤诱导基因RNR3结合Reporter综合遗传阵列方法，通过测定增加的Rnr3丰度来推断表现出基因组不稳定性的突变体。我们在未经处理的条件下和存在DNA破坏剂MMS的情况下，筛选了约4200个非必需突变酵母等位基因的基因组不稳定性。我们的结果为维持基因组所需的细胞过程和途径提供了广泛的见识。初步的后续工作表明，几个基因在维持基因组稳定性方面具有真正的作用。此外，我在两个高度正交的荧光成像平台上对两个屏幕进行了完整的比较，并比较了它们的可重复性和敏感性。

著录项

  • 作者

    Hendry, Jason Alexander.;

  • 作者单位

    University of Toronto (Canada).;

  • 授予单位 University of Toronto (Canada).;
  • 学科 Biochemistry.;Cellular biology.;Genetics.
  • 学位 M.Sc.
  • 年度 2015
  • 页码 108 p.
  • 总页数 108
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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