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dUTP incorporation into genomic DNA is linked to transcription in yeast

机译：dUTP掺入基因组DNA与酵母中的转录有关

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摘要

Highly activated transcription is associated with eukaryotic genome instability, resulting in increased rates of mitotic recombination and mutagenesis. The association between high transcription and genome stability is probably due to a variety of factors including an enhanced accumulation of DNA damage, transcription-associated supercoiling, collision between replication forks and the transcription machinery, and the persistence of RNA-DNA hybrids'. In the case of transcription-associated mutagenesis, we previously showed that there is a direct proportionality between the level of transcription and the mutation rate in the yeast Saccharomyces cerevisiae, and that the molecular nature of the mutations is affected by highly activated transcription. Here we show that the accumulation of apurinic/apyrimidinic sites is greatly enhanced in highly transcribed yeast DNA. We further demonstrate that most apurinic/apyrimidinic sites in highly transcribed DNA are derived from the removal of uracil, the presence of which is linked to direct incorporation of dUTP in place of dTTP. These results show an unexpected relationship between transcription and the fidelity of DNA synthesis, and raise intriguing cell biological issues with regard to nucleotide pool compartmentalization.
机译：高度激活的转录与真核基因组不稳定性相关，导致有丝分裂重组和诱变的速率增加。高转录与基因组稳定性之间的关联可能归因于多种因素，包括DNA损伤积累的增加，转录相关的超螺旋，复制叉与转录机制之间的碰撞以及RNA-DNA杂种的持久性。在与转录相关的诱变的情况下，我们以前表明，在酿酒酵母中，转录水平与突变率之间存在直接比例关系，并且突变的分子性质受高度激活的转录影响。在这里，我们显示在高度转录的酵母DNA中，嘌呤/嘧啶酮位点的积累大大增强。我们进一步证明，在高度转录的DNA中，大多数嘌呤/嘧啶定位点都来自尿嘧啶的去除，尿嘧啶的存在与dUTP代替dTTP的直接掺入有关。这些结果表明转录与DNA合成的保真度之间存在意想不到的关系，并且就核苷酸库区室化提出了令人感兴趣的细胞生物学问题。

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  • 来源
    《Nature》 |2009年第25期|1150-1153|共4页
  • 作者

    Nayun Kim; Sue Jinks-Robertson;

  • 作者单位

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.;

    Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, North Carolina 27710, USA.;

  • 收录信息 美国《科学引文索引》(SCI);美国《工程索引》(EI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
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