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

Research output: Contribution to journalArticle

294 Citations (Scopus)

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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Ribosomal DNA
Stem Cells
Yeasts
Chromosome Breakage
Proteins
Nuclear Proteins
Genome
Mutation
Genes

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., ... 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
Defossez, Pierre Antoine ; Prusty, Reeta ; Kaeberlein, Matt ; Lin, Su Ju ; Ferrigno, Paul ; Silver, Pamela A. ; Keil, Ralph L. ; Guarente, Leonard. / Elimination of replication block protein Fob1 extends the life span of yeast mother cells. In: Molecular cell. 1999 ; Vol. 3, No. 4. pp. 447-455.
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Defossez, PA, Prusty, R, Kaeberlein, M, Lin, SJ, Ferrigno, P, Silver, PA, Keil, RL & Guarente, L 1999, 'Elimination of replication block protein Fob1 extends the life span of yeast mother cells', Molecular cell, vol. 3, no. 4, pp. 447-455. https://doi.org/10.1016/S1097-2765(00)80472-4

Elimination of replication block protein Fob1 extends the life span of yeast mother cells. / Defossez, Pierre Antoine; Prusty, Reeta; Kaeberlein, Matt; Lin, Su Ju; Ferrigno, Paul; Silver, Pamela A.; Keil, Ralph L.; Guarente, Leonard.

In: Molecular cell, Vol. 3, No. 4, 04.1999, p. 447-455.

Research output: Contribution to journalArticle

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Defossez PA, Prusty R, Kaeberlein M, Lin SJ, Ferrigno P, Silver PA et al. Elimination of replication block protein Fob1 extends the life span of yeast mother cells. Molecular cell. 1999 Apr;3(4):447-455. https://doi.org/10.1016/S1097-2765(00)80472-4