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

doi:10.1016/S1097-2765(00)80472-4

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

Department of Biochemistry and Molecular Biology

Research output: Contribution to journal › Article › peer-review

343 Scopus citations

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 language	English (US)
Pages (from-to)	447-455
Number of pages	9
Journal	Molecular cell
Volume	3
Issue number	4
DOIs	https://doi.org/10.1016/S1097-2765(00)80472-4
State	Published - Apr 1999

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

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10.1016/S1097-2765(00)80472-4

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title = "Elimination of replication block protein Fob1 extends the life span of yeast mother cells",

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.",

author = "Defossez, {Pierre Antoine} and Reeta Prusty and Matt Kaeberlein and Lin, {Su Ju} and Paul Ferrigno and Silver, {Pamela A.} and Keil, {Ralph L.} and Leonard Guarente",

note = "Funding Information: We thank David Sinclair for reagents, Brad Johnson, Peter Park, David McNabb, and other members of the Guarente lab for insightful discussions, and Guillaume Adelmant and Ezra Aksoy for advice and support. This work was supported by NIH grants to L. G., P. A. S., and R. K. Funding Information: P.-A. D. was supported by INSERM and the Philippe Foundation, S. L. by a grant from the Anna Fuller Fund and the MIT Cancer Center, and P. F. by a Long-Term Fellowship from the HFSPO. ",

year = "1999",

month = apr,

doi = "10.1016/S1097-2765(00)80472-4",

language = "English (US)",

volume = "3",

pages = "447--455",

journal = "Molecular cell",

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T1 - Elimination of replication block protein Fob1 extends the life span of yeast mother cells

AU - Defossez, Pierre Antoine

AU - Prusty, Reeta

AU - Kaeberlein, Matt

AU - Lin, Su Ju

AU - Ferrigno, Paul

AU - Silver, Pamela A.

AU - Keil, Ralph L.

AU - Guarente, Leonard

N1 - Funding Information: We thank David Sinclair for reagents, Brad Johnson, Peter Park, David McNabb, and other members of the Guarente lab for insightful discussions, and Guillaume Adelmant and Ezra Aksoy for advice and support. This work was supported by NIH grants to L. G., P. A. S., and R. K. Funding Information: P.-A. D. was supported by INSERM and the Philippe Foundation, S. L. by a grant from the Anna Fuller Fund and the MIT Cancer Center, and P. F. by a Long-Term Fellowship from the HFSPO.

PY - 1999/4

Y1 - 1999/4

N2 - 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.

AB - 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.

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AN - SCOPUS:0033120871

SN - 1097-2765

VL - 3

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EP - 455

JO - Molecular cell

JF - Molecular cell

IS - 4

ER -

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

Abstract

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