The Duplicated Deacetylases Sir2 and Hst1 Subfunctionalized by Acquiring Complementary Inactivating Mutations

Froyd, Cara A.; Rusché, Laura N.

doi:10.1128/mcb.05175-11

Cited by 26 publications

(23 citation statements)

References 46 publications

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“…Consistent with this idea, KlSir2 complements an hst1⌬ deletion in S. cerevisiae (56) and partially suppresses a sir2⌬ mating defect (23). Studies of chimeric ScSir2-Hst1 molecules indicate that distinct regions of these deacetylases enable them to associate with the SIR or SUM1 complexes (41,56,80), and these interaction domains are conserved in KlSir2 (41). The most parsimonious model is that the ancestral Sir2 also utilized these interaction domains and that after duplication the paralogs acquired complementary inactivating mutations that reduced their affinities for one of the two complexes.…”

Section: Impact Of Gene Duplications On Silencing Proteinssupporting

confidence: 57%

Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage

2011

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The transcriptional silencing of the cryptic mating-type loci in Saccharomyces cerevisiae is one of the best-studied models of repressive heterochromatin. However, this type of heterochromatin, which is mediated by the Sir proteins, has a distinct molecular composition compared to the more ubiquitous type of heterochromatin found in Schizosaccharomyces pombe, other fungi, animals, and plants and characterized by the presence of HP1 (heterochromatin protein 1). This review discusses how the loss of important heterochromatin proteins, including HP1, in the budding yeast lineage presented an evolutionary opportunity for the development and diversification of alternative varieties of heterochromatin, in which the conserved deacetylase Sir2 and the replication protein Orc1 play key roles. In addition, we highlight how this diversification has been facilitated by gene duplications and has contributed to adaptations in lifestyle.

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Section: Impact Of Gene Duplications On Silencing Proteinssupporting

confidence: 57%

Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage

2011

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“…S. cerevisiae Hst1, in complex with Sum1 and Rfm1, functions in promoterspecific repression of middle-sporulation genes (47). K. lactis SIR2, another pre-whole-genome-duplication ortholog of S. cerevisiae SIR2 and HST1, possesses functions of both S. cerevisiae SIR2 and HST1 (9,48). Interestingly, T. delbrueckii orthologs of two middle-sporulation genes repressed by Hst1 in S. cerevisiae were derepressed in the T. delbrueckii sir2⌬ mutant: SPS4 and DIT1.…”

Section: Discussionmentioning

confidence: 99%

Evolution and Functional Trajectory of Sir1 in Gene Silencing

Ellahi

Rine

2016

Molecular and Cellular Biology

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We used the budding yeasts Saccharomyces cerevisiae and Torulaspora delbrueckii to examine the evolution of Sir-based silencing, focusing on Sir1, silencers, the molecular topography of silenced chromatin, and the roles of SIR and RNA interference (RNAi) genes in T. delbrueckii. Chromatin immunoprecipitation followed by deep sequencing (ChIP-Seq) analysis of Sir proteins in T. delbrueckii revealed a different topography of chromatin at the HML and HMR loci than was observed in S. cerevisiae. S. cerevisiae Sir1, enriched at the silencers of HML␣ and HMRa, was absent from telomeres and did not repress subtelomeric genes. In contrast to S. cerevisiae SIR1's partially dispensable role in silencing, the T. delbrueckii SIR1 paralog KOS3 was essential for silencing. KOS3 was also found at telomeres with T. delbrueckii Sir2 (Td-Sir2) and Td-Sir4 and repressed subtelomeric genes. Silencer mapping in T. delbrueckii revealed single silencers at HML and HMR, bound by Td-Kos3, Td-Sir2, and Td-Sir4. The KOS3 gene mapped near HMR, and its expression was regulated by Sir-based silencing, providing feedback regulation of a silencing protein by silencing. In contrast to the prominent role of Sir proteins in silencing, T. delbrueckii RNAi genes AGO1 and DCR1 did not function in heterochromatin formation. These results highlighted the shifting role of silencing genes and the diverse chromatin architectures underlying heterochromatin.

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“…In S96 and YJM789, Sir2p has a length of 562 amino acids (AA) but differs in five AA: P65T, V92E, D158V, K320N, and M424V. None of the five altered AA possesses an assigned function (Garcia and Pillus 2002; for review see Sauve et al 2006;Choy et al 2011;Froyd and Rusche 2011). Nevertheless, SIR2 was chosen as a candidate for gene swap experiments.…”

Section: Sir2 Is Part Of Qtlmentioning

confidence: 99%

Natural genetic variation in yeast longevity

et al. 2012

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The genetics of aging in the yeast Saccharomyces cerevisiae has involved the manipulation of individual genes in laboratory strains. We have instituted a quantitative genetic analysis of the yeast replicative lifespan by sampling the natural genetic variation in a wild yeast isolate. Haploid segregants from a cross between a common laboratory strain (S288c) and a clinically derived strain (YJM145) were subjected to quantitative trait locus (QTL) analysis, using 3048 molecular markers across the genome. Five significant, replicative lifespan QTL were identified. Among them, QTL 1 on chromosome IV has the largest effect and contains SIR2, whose product differs by five amino acids in the parental strains. Reciprocal gene swap experiments showed that this gene is responsible for the majority of the effect of this QTL on lifespan. The QTL with the second-largest effect on longevity was QTL 5 on chromosome XII, and the bulk of the underlying genomic sequence contains multiple copies (100-150) of the rDNA. Substitution of the rDNA clusters of the parental strains indicated that they play a predominant role in the effect of this QTL on longevity. This effect does not appear to simply be a function of extrachromosomal ribosomal DNA circle production. The results support an interaction between SIR2 and the rDNA locus, which does not completely explain the effect of these loci on longevity. This study provides a glimpse of the complex genetic architecture of replicative lifespan in yeast and of the potential role of genetic variation hitherto unsampled in the laboratory.

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The Duplicated Deacetylases Sir2 and Hst1 Subfunctionalized by Acquiring Complementary Inactivating Mutations

Cited by 26 publications

References 46 publications

Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage

Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage

Evolution and Functional Trajectory of Sir1 in Gene Silencing

Natural genetic variation in yeast longevity

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