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首页> 外文期刊>mSphere >Siz2 Prevents Ribosomal DNA Recombination by Modulating Levels of Tof2 in Saccharomyces cerevisiae
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Siz2 Prevents Ribosomal DNA Recombination by Modulating Levels of Tof2 in Saccharomyces cerevisiae

机译：Siz2通过调节酿酒酵母中的TOF2水平来防止核糖体DNA重组

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Ribosomal DNA (rDNA) recombination in budding yeast is regulated by multiple converging processes, including posttranslational modifications such as SUMOylation. In this study, we report that the absence of a SUMO E3 ligase, Siz2, results in increased unequal rDNA exchange. We show that Siz2 is enriched at the replication fork barrier (RFB) in the rDNA and also controls the homeostasis of Tof2 protein. siz2Δ resulted in increased accumulation of total Tof2 in the cell and a consequent increase in the enrichment of Tof2 at the rDNA. Overproducing Tof2 ectopically or conditional overexpression of Tof2 also resulted in higher levels of rDNA recombination, suggesting a direct role for Tof2. Additionally, our chromatin immunoprecipitation (ChIP) data indicate that the accumulation of Tof2 in a siz2Δ mutant resulted in an enhanced association of Fob1, an RFB binding protein at the rDNA at the RFB. This increased Fob1 association at the RFB may have resulted in the elevated rDNA recombination. Our study thus demonstrates that the Tof2 levels modulate recombination at the rDNA. IMPORTANCE The genes that encode rRNA in Saccharomyces cerevisiae are organized as multiple repeats. The repetitive nature and heavy transcription of this region make it prone to DNA breaks. DNA breaks could lead to recombination, which could result in either loss or gain of repeats with detrimental consequences to the cell. Multiple mechanisms operate to maintain the stability of rDNA. Earlier studies reported that the absence of Ulp2, a deSUMOylase, resulted in declining levels of Tof2 and thereby disrupted rDNA silencing. In contrast, our findings suggest that accumulation of Tof2 can also result in increased rDNA recombination, through a mechanism that involves Fob1, an RFB-bound protein. While our study has examined only Tof2, rDNA recombination could be regulated by other proteins through a mechanism similar to this.
机译：芽孢芽酵母中的核糖体DNA（RDNA）重组由多种会聚方法调节，包括诸如SuMoylation的后期改性。在这项研究中，我们报告说，没有SUMO E3连接酶SIZ2，导致增加不等的RDNA交换。我们表明Siz2在RDNA中的复制叉屏障（RFB）中富集，并控制TOF2蛋白的稳态。 SiZ2δ导致细胞中总TOF2的积累增加，因此rDNA在rDNA中的富集TOF2的增加。超越TOF2不同的TOF2的过表达也导致较高水平的RDNA重组，表明TOF2的直接作用。另外，我们的染色质免疫沉淀（芯片）数据表明，SiZ2δ突变体中TOF2的积累导致FOB1的增强型缔合A，RFB在RFB处的RFB结合蛋白。在RFB的这种增加的FOB1关联可能导致升高的RDNA重组。因此，我们的研究表明TOF2水平调节RDNA的重组。重视编码酿酒酵母中RRNA的基因被组织为多重重复。该区域的重复性和重转录使其容易发生DNA断裂。 DNA断裂可能导致重组，这可能导致对细胞的不利后果导致重复的损失或增益。多种机制操作以保持RDNA的稳定性。早期的研究报道说，没有ULP2，脱佛浴酶导致TOF2水平下降，从而破坏RDNA沉默。相比之下，我们的研究结果表明TOF2的积累也可以通过涉及FOB1，RFB结合蛋白的机制导致RDNA重组增加。虽然我们的研究仅检查了TOF2，但是RDNA重组可以通过类似于此的机制来调节其他蛋白质。

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