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      Genetic manipulation of longevity-related genes as a tool to regulate yeast life span and metabolite production during winemaking.

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          Abstract

          Yeast viability and vitality are essential for different industrial processes where the yeast Saccharomyces cerevisiae is used as a biotechnological tool. Therefore, the decline of yeast biological functions during aging may compromise their successful biotechnological use. Life span is controlled by a variety of molecular mechanisms, many of which are connected to stress tolerance and genomic stability, although the metabolic status of a cell has proven a main factor affecting its longevity. Acetic acid and ethanol accumulation shorten chronological life span (CLS), while glycerol extends it.

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          A new efficient gene disruption cassette for repeated use in budding yeast.

          U Güldener, S. Heck, T Fielder … (1996)
          The dominant kanr marker gene plays an important role in gene disruption experiments in budding yeast, as this marker can be used in a variety of yeast strains lacking the conventional yeast markers. We have developed a loxP-kanMX-loxP gene disruption cassette, which combines the advantages of the heterologous kanr marker with those from the Cre-lox P recombination system. This disruption cassette integrates with high efficiency via homologous integration at the correct genomic locus (routinely 70%). Upon expression of the Cre recombinase the kanMX module is excised by an efficient recombination between the loxP sites, leaving behind a single loxP site at the chromosomal locus. This system allows repeated use of the kanr marker gene and will be of great advantage for the functional analysis of gene families.
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            Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.

            S Lin, P A Defossez, L Guarente (2000)
            Calorie restriction extends life-span in a wide variety of organisms. Although it has been suggested that calorie restriction may work by reducing the levels of reactive oxygen species produced during respiration, the mechanism by which this regimen slows aging is uncertain. Here, we mimicked calorie restriction in yeast by physiological or genetic means and showed a substantial extension in life-span. This extension was not observed in strains mutant for SIR2 (which encodes the silencing protein Sir2p) or NPT1 (a gene in a pathway in the synthesis of NAD, the oxidized form of nicotinamide adenine dinucleotide). These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD.
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              Histone H4 lysine-16 acetylation regulates cellular lifespan

              Weiwei Dang, Kristan Steffen, Rocco Perry … (2009)
              Cells undergoing developmental processes are characterized by persistent non-genetic alterations in chromatin, termed epigenetic changes, represented by distinct patterns of DNA methylation and histone post-translational modifications. Sirtuins, a group of conserved NAD+-dependent deacetylases or ADP-ribosylases, promote longevity in diverse organisms; however, their molecular mechanisms in aging regulation remain poorly understood. Yeast Sir2, the founding member of the family, establishes and maintains chromatin silencing by removing H4 lysine 16 acetylation and bringing in other silencing proteins. Here we show an age-associated decrease in Sir2 protein abundance accompanied by an increase in H4 lysine 16 acetylation and loss of histones at specific subtelomeric regions in replicatively old yeast cells, which results in compromised transcriptional silencing at these loci. Antagonizing activities of Sir2 and Sas2, a histone acetyltransferase, regulate the replicative lifespan through histone H4 lysine 16 at subtelomeric regions. This pathway, distinct from existing aging models for yeast, may represent an evolutionarily conserved function of Sirtuins in regulation of replicative aging by maintenance of intact telomeric chromatin.
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                Author and article information

                Journal
                Journal ID (iso-abbrev): Microb Cell Fact
                Title: Microbial cell factories
                Publisher: Springer Science and Business Media LLC
                ISSN (Electronic): 1475-2859
                ISSN (Print): 1475-2859
                Publication date (Electronic): Jan 02 2013
                Volume: 12
                Affiliations
                [1 ] Departamento de Biotecnología, Instituto de Agroquímica y Tecnología de Alimentos-CSIC, Av, Agustín Escardino, 7, Paterna 46980, Spain.
                Article
                Publisher Item ID: 1475-2859-12-1
                DOI: 10.1186/1475-2859-12-1
                PMC ID: 3583744
                PubMed ID: 23282100
                SO-VID: a78dd169-40cf-454a-924a-88b5f9670f1c
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