Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae

Brian K. Kennedy; Monica Gotta; David A. Sinclair; Kevin Mills; David S. McNabb; Mala Murthy; Sally M. Pak; Thierry Laroche; Susan M. Gasser; Leonard Guarente

doi:10.1016/S0092-8674(00)80219-6

Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae

Brian K. Kennedy, Monica Gotta, David A. Sinclair, Kevin Mills, David S. McNabb, Mala Murthy, Sally M. Pak, Thierry Laroche, Susan M. Gasser, Leonard Guarente

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

339 Scopus citations

Abstract

A prior genetic study indicated that activity of Sir silencing proteins at a hypothetical AGE locus is essential for long life span. In this model, the SIR4-42 mutation would direct the Sir protein complex to the AGE locus, giving rise to a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this relocalization is dependent on both UTH4 a novel yeast gene that extends life span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is the AGE locus and that nucleolar function is compromised in old yeast cells in a way that may be mitigated by targeting of Sir proteins to the nucleolus.

Original language	English (US)
Pages (from-to)	381-391
Number of pages	11
Journal	Cell
Volume	89
Issue number	3
DOIs	https://doi.org/10.1016/S0092-8674(00)80219-6
State	Published - May 2 1997
Externally published	Yes

All Science Journal Classification (ASJC) codes

General Biochemistry, Genetics and Molecular Biology

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10.1016/S0092-8674(00)80219-6

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title = "Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae",

abstract = "A prior genetic study indicated that activity of Sir silencing proteins at a hypothetical AGE locus is essential for long life span. In this model, the SIR4-42 mutation would direct the Sir protein complex to the AGE locus, giving rise to a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this relocalization is dependent on both UTH4 a novel yeast gene that extends life span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is the AGE locus and that nucleolar function is compromised in old yeast cells in a way that may be mitigated by targeting of Sir proteins to the nucleolus.",

author = "Kennedy, {Brian K.} and Monica Gotta and Sinclair, {David A.} and Kevin Mills and McNabb, {David S.} and Mala Murthy and Pak, {Sally M.} and Thierry Laroche and Gasser, {Susan M.} and Leonard Guarente",

note = "Funding Information: We thank N. Silverman and Y.-H. Tu for technical advice, J. Zhang for constructing the library used to clone UTH4, and members of the Gasser and Guarente laboratories for helpful insights. We also thank Ed Hurt for anti-Nop1p antiserum, Oscar Aparicio for pURADE2, and Gerry Fink for pNL47. D. S. was supported by a Helen Hay Whitney postdoctoral fellowship; K. M., by a National Institutes of Health predoctoral training grant. The Guarente lab is supported by a National Institutes of Health grant (AG11119). S. Gasser thanks the Swiss National Science Foundation, Human Frontiers, and the Swiss Institute for Experimental Cancer Research for support.",

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doi = "10.1016/S0092-8674(00)80219-6",

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T1 - Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae

AU - Kennedy, Brian K.

AU - Gotta, Monica

AU - Sinclair, David A.

AU - Mills, Kevin

AU - McNabb, David S.

AU - Murthy, Mala

AU - Pak, Sally M.

AU - Laroche, Thierry

AU - Gasser, Susan M.

AU - Guarente, Leonard

N1 - Funding Information: We thank N. Silverman and Y.-H. Tu for technical advice, J. Zhang for constructing the library used to clone UTH4, and members of the Gasser and Guarente laboratories for helpful insights. We also thank Ed Hurt for anti-Nop1p antiserum, Oscar Aparicio for pURADE2, and Gerry Fink for pNL47. D. S. was supported by a Helen Hay Whitney postdoctoral fellowship; K. M., by a National Institutes of Health predoctoral training grant. The Guarente lab is supported by a National Institutes of Health grant (AG11119). S. Gasser thanks the Swiss National Science Foundation, Human Frontiers, and the Swiss Institute for Experimental Cancer Research for support.

PY - 1997/5/2

Y1 - 1997/5/2

N2 - A prior genetic study indicated that activity of Sir silencing proteins at a hypothetical AGE locus is essential for long life span. In this model, the SIR4-42 mutation would direct the Sir protein complex to the AGE locus, giving rise to a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this relocalization is dependent on both UTH4 a novel yeast gene that extends life span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is the AGE locus and that nucleolar function is compromised in old yeast cells in a way that may be mitigated by targeting of Sir proteins to the nucleolus.

AB - A prior genetic study indicated that activity of Sir silencing proteins at a hypothetical AGE locus is essential for long life span. In this model, the SIR4-42 mutation would direct the Sir protein complex to the AGE locus, giving rise to a long life span. We show by indirect immunofluorescence that Sir3p and Sir4p are redirected to the nucleolus in the SIR4-42 mutant. Furthermore, this relocalization is dependent on both UTH4 a novel yeast gene that extends life span, and its homologue YGL023. Strikingly, the Sir complex is relocalized from telomeres to the nucleolus in old wild-type cells. We propose that the rDNA is the AGE locus and that nucleolar function is compromised in old yeast cells in a way that may be mitigated by targeting of Sir proteins to the nucleolus.

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Redistribution of silencing proteins from telomeres to the nucleolus is associated with extension of life span in S. cerevisiae

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