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Differential regulation of two closely clustered yeast genes MAG1 and DDI1 by cell-cycle checkpoints.

机译:细胞周期检查点对两个紧密聚集的酵母基因MAG1和DDI1的差异调节。

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摘要

Eukaryotic DNA-damage checkpoint genes have been shown to not only arrest cells at certain stages, but are also involved in the transcriptional response to DNA damage. However, while the signal transduction for cell-cycle checkpoint is well characterized, it is not clear whether the same signal transduction pathway is responsible for the regulation of all DNA damage-inducible genes. In order to understand how different checkpoint genes are involved in gene regulation, the effects of various checkpoint mutations on the expression of a unique yeast MAG1 - DDI1 dual promoter were examined in this study. MAG1 and DDI1 are transcribed from a common promoter region and co-induced by a variety of DNA damaging agents. However, gene-specific cis -acting elements were also identified, and the two genes are indeed differentially expressed under certain conditions. We found that DDI1 induction was not affected in any of the checkpoint mutants. In contrast, MAG1 induction was completely abolished in the pol2 and rad53 mutants. However, in the mec1-1 or any of the G1/S and G2/M checkpoint mutants, including rad9, rad17 and rad24, DNA damage-induced MAG1 expression was not significantly affected, and a rad9 rad17 double mutation only slightly reduced MAG1 induction. Based on this and previous studies, we present two models for the role of checkpoint genes in transcriptional regulation in response to DNA damage.
机译:真核生物的DNA损伤检查点基因不仅能在某些阶段阻止细胞,而且还参与了对DNA损伤的转录反应。然而,尽管细胞周期检查点的信号转导已被很好地表征,但尚不清楚同一信号转导途径是否负责所有DNA损伤诱导基因的调控。为了了解不同的检查点基因如何参与基因调控,在本研究中检查了各种检查点突变对独特的酵母MAG1-DDI1双启动子表达的影响。 MAG1和DDI1从共同的启动子区域转录,并被多种DNA破坏剂共同诱导。然而,还鉴定了基因特异性的顺式作用元件,并且在某些条件下,这两个基因确实差异表达。我们发现,在任何检查点突变体中,DDI1诱导均不受影响。相反,在pol2和rad53突变体中,MAG1诱导被完全消除。但是,在mec1-1或任何G1 / S和G2 / M检查点突变体中,包括rad9,rad17和rad24,DNA损伤诱导的MAG1表达均未受到显着影响,而rad9 rad17双重突变仅轻微降低了MAG1诱导。 。基于此研究和先前的研究,我们提出了两个检查点基因在响应DNA损伤的转录调控中的作用的模型。

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