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首页> 外文期刊>Nature >Coordinated control of replication and transcription by a SAPK protects genomic integrity
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Coordinated control of replication and transcription by a SAPK protects genomic integrity

机译：SAPK对复制和转录的协调控制可保护基因组完整性

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摘要

Upon environmental changes or extracellular signals, cells are subjected to marked changes in gene expression . Dealing with high levels of transcription during replication is critical to prevent collisions between the transcription and replication pathways and avoid recombination events. In response to osmostress, hundreds of stress-responsive genes are rapidly induced by the stress-activated protein kinase (SAPK) Hogl (ref. 6), even during S phase. Here we show in Saccharomyces cerevisae that a single signalling molecule, Hogl, coordinates both replication and transcription upon osmostress. Hogl interacts with and phosphorylates Mrcl, a component of the replication complex. Phosphorylation occurs at different sites to those targeted by Mecl upon DNA damage. Mrcl phosphorylation by Hogl delays early and late origin firing by preventing Cdc45 loading, as well as slowing down replication-complex progression. Regulation of Mrcl by Hogl is completely independent of Mecl and Rad53. Cells carrying a non-phosphorylatable allele of MRC1 (mrcl~(3A)) do not delay replication upon stress and show a marked increase in transcription-associated recombination, genomic instability and Rad52 foci. In contrast, mrcl~(3A) induces Rad53 and survival in the presence of hydroxyurea or methyl metha-nesulphonate. Therefore, Hogl and Mrcl define a novel S-phase checkpoint independent of the DNA-damage checkpoint that permits eukaryotic cells to prevent conflicts between DNA replication and transcription, which would otherwise lead to genomic instability when both phenomena are temporally coincident.
机译：在环境变化或细胞外信号作用下，细胞的基因表达会发生明显变化。复制过程中处理高水平的转录对于防止转录和复制途径之间的冲突以及避免重组事件至关重要。响应渗透压，即使在S期，应力激活蛋白激酶（SAPK）Hogl也会迅速诱导成百上千个压力响应基因（参考文献6）。在这里，我们在酿酒酵母中显示，单个信号分子Hogl可以调节渗透压下的复制和转录。 Hogl与复制复合物的成分Mrcl相互作用并使其磷酸化。磷酸化发生在与DNA受损时Mecl靶向的位置不同的位置。 Hogl产生的Mrcl磷酸化可通过阻止Cdc45加载来延迟早期和晚期起始放电，并减慢复制复合物的进程。 Hogl对Mrcl的调控完全独立于Mecl和Rad53。携带MRC1（mrcl〜（3A））的非磷酸化等位基因的细胞在压力下不会延迟复制，并且在转录相关重组，基因组不稳定性和Rad52病灶方面显示出明显的增加。相反，mrcl_（3A）在羟基脲或甲基甲磺酸钠存在下诱导Rad53的存活。因此，Hogl和Mrcl定义了一个独立于DNA损伤检查点的新型S期检查点，该检查点允许真核细胞防止DNA复制和转录之间的冲突，否则当两种现象在时间上同时发生时，这将导致基因组不稳定。

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  • 来源
    《Nature》 |2013年第7430期|116-119|共4页
  • 作者

    Alba Duch; Irene Felipe-Abrio; Sonia Barroso; Gilad Yaakov; Maria Garcia-Rubio; Andres Aguilera; Eulalia de Nadal; Francesc Posas;

  • 作者单位

    Cell Signaling Unit, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), Barcelona E-08003, Spain;

    Centro Andaluz de Biologia Molecular and Medicina Regenerativa CABIMER, Universidad de Sevilla, 41092 Sevilla, Spain;

    Centro Andaluz de Biologia Molecular and Medicina Regenerativa CABIMER, Universidad de Sevilla, 41092 Sevilla, Spain;

    Cell Signaling Unit, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), Barcelona E-08003, Spain;

    Centro Andaluz de Biologia Molecular and Medicina Regenerativa CABIMER, Universidad de Sevilla, 41092 Sevilla, Spain;

    Centro Andaluz de Biologia Molecular and Medicina Regenerativa CABIMER, Universidad de Sevilla, 41092 Sevilla, Spain;

    Cell Signaling Unit, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), Barcelona E-08003, Spain;

    Cell Signaling Unit, Departament de Ciencies Experimentals i de la Salut, Universitat Pompeu Fabra (UPF), Barcelona E-08003, Spain;

  • 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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