The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms
The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type infor...
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| Veröffentlicht in: | Genes & development 1999-10, Vol.13 (19), p.2570-2580 |
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| creator | Kaeberlein, M McVey, M Guarente, L |
| description | The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed. |
| doi_str_mv | 10.1101/gad.13.19.2570 |
| format | Article |
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Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed.</description><identifier>ISSN: 0890-9369</identifier><identifier>DOI: 10.1101/gad.13.19.2570</identifier><identifier>PMID: 10521401</identifier><language>eng</language><publisher>United States: Cold Spring Harbor Laboratory Press</publisher><subject>DNA, Fungal ; DNA, Ribosomal ; DNA-Binding Proteins - genetics ; DNA-Binding Proteins - physiology ; Fungal Proteins - genetics ; Fungal Proteins - physiology ; Histone Deacetylases ; Mating Factor ; Mutagenesis ; Peptides ; Phenotype ; Research Paper ; Saccharomyces cerevisiae ; Saccharomyces cerevisiae - genetics ; Saccharomyces cerevisiae - physiology ; Saccharomyces cerevisiae Proteins ; Silent Information Regulator Proteins, Saccharomyces cerevisiae ; Sirtuin 2 ; Sirtuins ; Trans-Activators - genetics ; Trans-Activators - physiology</subject><ispartof>Genes & development, 1999-10, Vol.13 (19), p.2570-2580</ispartof><rights>Copyright © 1999, Cold Spring Harbor Laboratory Press 1999</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-15e5ade32711915fdadae93b01364351d9239a0496325d86ae6f1d6e9be24b9d3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC317077/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC317077/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,315,728,781,785,886,27928,27929,53795,53797</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10521401$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kaeberlein, M</creatorcontrib><creatorcontrib>McVey, M</creatorcontrib><creatorcontrib>Guarente, L</creatorcontrib><title>The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms</title><title>Genes & development</title><addtitle>Genes Dev</addtitle><description>The SIR genes are determinants of life span in yeast mother cells. Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. 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Here we show that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining. The short life span of a sir3 or sir4 mutant is due to the simultaneous expression of a and alpha mating-type information, which indirectly causes an increase in rDNA recombination and likely increases the production of extrachromosomal rDNA circles. The short life span of a sir2 mutant also reveals a direct failure to repress recombination generated by the Fob1p-mediated replication block in the rDNA. Sir2p is a limiting component in promoting yeast longevity, and increasing the gene dosage extends the life span in wild-type cells. A possible role of the conserved SIR2 in mammalian aging is discussed.</abstract><cop>United States</cop><pub>Cold Spring Harbor Laboratory Press</pub><pmid>10521401</pmid><doi>10.1101/gad.13.19.2570</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Genes & development, 1999-10, Vol.13 (19), p.2570-2580 |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | DNA, Fungal DNA, Ribosomal DNA-Binding Proteins - genetics DNA-Binding Proteins - physiology Fungal Proteins - genetics Fungal Proteins - physiology Histone Deacetylases Mating Factor Mutagenesis Peptides Phenotype Research Paper Saccharomyces cerevisiae Saccharomyces cerevisiae - genetics Saccharomyces cerevisiae - physiology Saccharomyces cerevisiae Proteins Silent Information Regulator Proteins, Saccharomyces cerevisiae Sirtuin 2 Sirtuins Trans-Activators - genetics Trans-Activators - physiology |
| title | The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms |
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