Departments of Biochemistry & Molecular Biology and Oncology, Robson DNA Science Centre, Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB, Canada.
Department of Biochemistry, Microbiology and Immunology, University of Saskatchewan, Saskatoon, SK, Canada.
Aging Cell. 2021 Jun;20(6):e13373. doi: 10.1111/acel.13373. Epub 2021 May 12.
The ribosomal DNA (rDNA) in Saccharomyces cerevisiae is in one tandem repeat array on Chromosome XII. Two regions within each repetitive element, called intergenic spacer 1 (IGS1) and IGS2, are important for organizing the rDNA within the nucleolus. The Smc5/6 complex localizes to IGS1 and IGS2. We show that Smc5/6 has a function in the rDNA beyond its role in homologous recombination (HR) at the replication fork barrier (RFB) located in IGS1. Fob1 is required for optimal binding of Smc5/6 at IGS1 whereas the canonical silencing factor Sir2 is required for its optimal binding at IGS2, independently of Fob1. Through interdependent interactions, Smc5/6 stabilizes Sir2 and Cohibin at both IGS and its recovery at IGS2 is important for nucleolar compaction and transcriptional silencing, which in turn supports rDNA stability and lifespan.
酿酒酵母的核糖体 DNA(rDNA)位于染色体 XII 的一个串联重复阵列上。每个重复元件内的两个区域,称为基因间间隔区 1(IGS1)和 IGS2,对于核仁内 rDNA 的组织至关重要。Smc5/6 复合物定位于 IGS1 和 IGS2。我们表明,Smc5/6 在复制叉障碍(RFB)处的同源重组(HR)之外,在 rDNA 中具有功能,该 RFB 位于 IGS1 中。Fob1 对于 Smc5/6 在 IGS1 上的最佳结合是必需的,而典型的沉默因子 Sir2 对于其在 IGS2 上的最佳结合是必需的,而与 Fob1 无关。通过相互依存的相互作用,Smc5/6 稳定了 Sir2 和 Cohibin,在 IGS 及其在 IGS2 上的恢复对于核仁紧缩和转录沉默很重要,这反过来又支持 rDNA 的稳定性和寿命。