Defossez P A, Prusty R, Kaeberlein M, Lin S J, Ferrigno P, Silver P A, Keil R L, Guarente L
Department of Biology Massachusetts Institute of Technology, Cambridge, 02139, USA.
Mol Cell. 1999 Apr;3(4):447-55. doi: 10.1016/s1097-2765(00)80472-4.
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.
酵母衰老的一个原因是基因组中100 - 200个串联重复拷贝产生的核糖体DNA（rDNA）环状物种的积累。我们在此表明，FOB1基因突变会减缓这些环的产生，从而延长寿命。已知Fob1p会在rDNA中对复制叉形成单向阻断。我们表明Fob1p是一种核仁蛋白，这表明它直接参与了复制叉阻断。我们提出，这种阻断可通过导致染色体断裂引发衰老，而染色体断裂的修复会导致rDNA环的产生。这些发现可能为酵母以及或许高等生物的代谢率与衰老之间提供一种新的联系。
