Elimination of replication block protein Fob1 extends the life span of yeast mother cells

Pierre Antoine Defossez, Reeta Prusty, Matt Kaeberlein, Su Ju Lin, Paul Ferrigno, Pamela A. Silver, Ralph L. Keil, Leonard Guarente

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)447-455
Number of pages9
JournalMolecular cell
Volume3
Issue number4
DOIs
StatePublished - Apr 1999

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All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Defossez, P. A., Prusty, R., Kaeberlein, M., Lin, S. J., Ferrigno, P., Silver, P. A., Keil, R. L., & Guarente, L. (1999). Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Molecular cell, 3(4), 447-455. https://doi.org/10.1016/S1097-2765(00)80472-4