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出芽酵母黏连蛋白装载因子Scc2的失活会在全局层面以及对单个DNA双链断裂作出反应时改变基因表达。

Inactivation of the budding yeast cohesin loader Scc2 alters gene expression both globally and in response to a single DNA double strand break.

作者信息

Lindgren Emma, Hägg Sara, Giordano Fosco, Björkegren Johan, Ström Lena

机构信息

a Department of Cell and Molecular Biology; Karolinska Institutet ; Stockholm , Sweden.

出版信息

Cell Cycle. 2014;13(23):3645-58. doi: 10.4161/15384101.2014.964108.

Abstract

Genome integrity is fundamental for cell survival and cell cycle progression. Important mechanisms for keeping the genome intact are proper sister chromatid segregation, correct gene regulation and efficient repair of damaged DNA. Cohesin and its DNA loader, the Scc2/4 complex have been implicated in all these cellular actions. The gene regulation role has been described in several organisms. In yeast it has been suggested that the proteins in the cohesin network would effect transcription based on its role as insulator. More recently, data are emerging indicating direct roles for gene regulation also in yeast. Here we extend these studies by investigating whether the cohesin loader Scc2 is involved in regulation of gene expression. We performed global gene expression profiling in the absence and presence of DNA damage, in wild type and Scc2 deficient G2/M arrested cells, when it is known that Scc2 is important for DNA double strand break repair and formation of damage induced cohesion. We found that not only the DNA damage specific transcriptional response is distorted after inactivation of Scc2 but also the overall transcription profile. Interestingly, these alterations did not correlate with changes in cohesin binding.

摘要

基因组完整性对于细胞存活和细胞周期进程至关重要。维持基因组完整的重要机制包括正确的姐妹染色单体分离、正确的基因调控以及受损DNA的有效修复。黏连蛋白及其DNA装载因子Scc2/4复合物参与了所有这些细胞活动。基因调控作用已在多种生物体中得到描述。在酵母中,有人提出黏连蛋白网络中的蛋白质基于其作为绝缘体的作用会影响转录。最近,越来越多的数据表明基因调控在酵母中也具有直接作用。在这里,我们通过研究黏连蛋白装载因子Scc2是否参与基因表达调控来扩展这些研究。我们在野生型和Scc2缺陷的G2/M期阻滞细胞中,分别在不存在和存在DNA损伤的情况下进行了全基因组基因表达谱分析,已知Scc2对DNA双链断裂修复和损伤诱导的黏连形成很重要。我们发现,Scc2失活后不仅DNA损伤特异性转录反应会扭曲,而且整体转录谱也会改变。有趣的是,这些改变与黏连蛋白结合的变化无关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/866c/4612677/42e612280d66/kccy-13-23-964108-g001.jpg

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