Elimination of replication block protein Fob1 extends the life span of yeast mother cells
Elimination of replication block protein Fob1 extends the life span of yeast mother cells
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DOI：
10.1016/s1097-2765(00)80472-4
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发表时间：
1999-04-01
期刊：
影响因子：
16
通讯作者：
Guarente, L
中科院分区：
文献类型：
--
作者：
Defossez, PA;Prusty, R;Guarente, L
酵母衰老的原因之一是由基因组中100-200个串联重复拷贝产生的核糖体DNA（rDNA）环状种类的积累。我们在这里表明，FOB 1基因的突变减缓了这些圆圈的产生，从而延长了寿命。已知Fob 1 p在rDNA中创建复制叉的单向阻断。我们发现，Fob 1 p是一个核仁蛋白，这表明直接参与复制叉块。我们认为，这种阻断可以通过引起染色体断裂来触发衰老，而染色体断裂的修复导致rDNA环的产生。这些发现可能提供了一个新的联系代谢率和老化的酵母，也许，高等生物。
A cause of aging in yeast is the accumulation of circular species of ribosomal DNA (rDNA) arising from the 100-200 tandemly repeated copies in the genome. We show here that mutation of the FOB1 gene slows the generation of these circles and thus extends life span. Fob1p is known to create a unidirectional block to replication forks in the rDNA. We show that Fob1p is a nucleolar protein, suggesting a direct involvement in the replication fork block. We propose that this block can trigger aging by causing chromosomal breaks, the repair of which results in the generation of rDNA circles. These findings may provide a novel link between metabolic rate and aging in yeast and, perhaps, higher organisms.