National Institute of Genetics, Sokendai, 1111 Yata, Mishima, 411-8540 Japan.
Science. 2010 Feb 5;327(5966):693-6. doi: 10.1126/science.1179044.
The ribosomal RNA (rDNA) gene repeats are essential housekeeping genes found in all organisms. A gene amplification system maintains large cluster(s) of tandemly repeated copies in the chromosome, with each species having a specific number of copies. Yeast has many untranscribed rDNA copies (extra copies), and we found that when they are lost, the cells become sensitive to DNA damage induced by mutagens. We show that this sensitivity is dependent on rDNA transcriptional activity, which interferes with cohesion between rDNA loci of sister chromatids. The extra rDNA copies facilitate condensin association and sister-chromatid cohesion, thereby facilitating recombinational repair. These results suggest that high concentrations of heavily transcribed genes are toxic to the cells, and therefore amplified genes, such as rDNA, have evolved.
核糖体 RNA(rDNA)基因重复是所有生物中必需的管家基因。基因扩增系统在染色体中维持着大量串联重复拷贝的簇，每个物种都有特定数量的拷贝。酵母有许多未转录的 rDNA 拷贝（额外的拷贝），我们发现当它们丢失时，细胞对诱变剂诱导的 DNA 损伤变得敏感。我们表明，这种敏感性依赖于 rDNA 的转录活性，它干扰了姐妹染色单体上 rDNA 位点之间的着丝粒。额外的 rDNA 拷贝促进了凝聚素的结合和姐妹染色单体的黏合，从而促进了重组修复。这些结果表明，高度转录的基因浓度过高对细胞是有毒的，因此扩增基因，如 rDNA，已经进化。
