A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription
A novel role for the budding yeast RAD9 checkpoint gene in DNA damage-dependent transcription
复制标题
DOI：
10.1002/j.1460-2075.1996.tb00765.x
复制
发表时间：
1996-08-01
期刊：
影响因子：
11.4
通讯作者：
Lowndes, NF
中科院分区：
文献类型：
--
作者：
Aboussekhra, A;Vialard, JE;Lowndes, NF
细胞通过阻止细胞周期进程和激活几种DNA修复机制来响应DNA损伤。这些反应使受损的DNA得到有效修复，从而确保遗传完整性的维持。在芽殖酵母（酿酒酵母）中，DNA损伤导致细胞周期G（1）、S和G（2）期检查点的激活和转录反应。G（1）和G（2）检查点先前已被证明是在RAD 9基因的控制下。我们在这里表明，RAD 9也需要对DNA损伤的转录反应。北方印迹分析表明，RAD 9控制DNA损伤特异性诱导修复，复制和重组基因的大'调节子'。这种诱导是细胞周期非依赖性的，因为它在异步培养物中观察到，并且细胞被阻断在G（1）或G（2）/M中，在基于lacZ标记的质粒测定中也从分离的损伤应答启动子元件观察到RAD 9依赖性诱导。在转录反应中缺陷的rad 9细胞比野生型细胞对DNA损伤更敏感，即使在检查点的功能取代后，这表明这种激活可能在DNA修复中具有重要作用。我们的研究结果与大肠杆菌SOS系统平行观察，并建议存在一个类似的真核网络协调细胞对DNA损伤的反应。
Cells respond to DNA damage by arresting cell cycle progression and activating several DNA repair mechanisms. These responses allow damaged DNA to be repaired efficiently, thus ensuring the maintenance of genetic integrity. In the budding yeast, Saccharomyces cerevisiae, DNA damage leads both to activation of checkpoints at the G(1), S and G(2) phases of the cell cycle and to a transcriptional response. The G(1) and G(2) checkpoints have been shown previously to be under the control of the RAD9 gene. We show here that RAD9 is also required for the transcriptional response to DNA damage. Northern blot analysis demonstrated that RAD9 controls the DNA damage-specific induction of a large 'regulon' of repair, replication and recombination genes. This induction is cell cycle-independent as it was observed in asynchronous cultures and cells blocked in G(1) or G(2)/M, RAD9-dependent induction was also observed from isolated damage responsive promoter elements in a lacZ reporter-based plasmid assay. rad9 cells deficient in the transcriptional response were more sensitive to DNA damage than wild-type cells, even after functional substitution of checkpoints, suggesting that this activation may have an important role in DNA repair. Our findings parallel observations with the Escherichia coli SOS system and suggest the existence of an analogous eukaryotic network coordinating the cellular responses to DNA damage.