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Intragenic repeat e...
Intragenic repeat expansion in the cell wall protein gene HPF1 controls yeast chronological aging
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Barré, Benjamin P. (author)
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Hallin, Johan (author)
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Yue, Jia Xing (author)
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- Persson, Karl, 1988 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Mikhalev, Ekaterina (author)
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Irizar, Agurtzane (author)
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Holt, Sylvester (author)
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Thompson, Dawn (author)
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- Molin, Mikael, 1973 (author)
- Chalmers tekniska högskola,Chalmers University of Technology
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- Warringer, Jonas, 1973 (author)
- Gothenburg University,Göteborgs universitet,Institutionen för kemi och molekylärbiologi,Department of Chemistry and Molecular Biology
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Liti, Gianni (author)
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(creator_code:org_t)
- 2020-04-10
- 2020
- English.
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In: Genome Research. - : Cold Spring Harbor Laboratory. - 1088-9051 .- 1549-5469. ; 30:5, s. 697-710
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https://research.cha... (primary) (free)
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https://genome.cshlp...
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https://doi.org/10.1...
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https://gup.ub.gu.se...
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Abstract
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- Aging varies among individuals due to both genetics and environment, but the underlying molecular mechanisms remain largely unknown. Using a highly recombined Saccharomyces cerevisiae population, we found 30 distinct quantitative trait loci (QTLs) that control chronological life span (CLS) in calorie-rich and calorie-restricted environments and under rapamycin exposure. Calorie restriction and rapamycin extended life span in virtually all genotypes but through different genetic variants. We tracked the two major QTLs to the cell wall glycoprotein genes FLO11 and HPF1. We found that massive expansion of intragenic tandem repeats within the N-terminal domain of HPF1 was sufficient to cause pronounced life span shortening. Life span impairment by HPF1 was buffered by rapamycin but not by calorie restriction. The HPF1 repeat expansion shifted yeast cells from a sedentary to a buoyant state, thereby increasing their exposure to surrounding oxygen. The higher oxygenation altered methionine, lipid, and purine metabolism, and inhibited quiescence, which explains the life span shortening. We conclude that fast-evolving intragenic repeat expansions can fundamentally change the relationship between cells and their environment with profound effects on cellular lifestyle and longevity.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Genetik (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Genetics (hsv//eng)
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
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- By the author/editor
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Barré, Benjamin ...
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Hallin, Johan
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Yue, Jia Xing
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Persson, Karl, 1 ...
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Mikhalev, Ekater ...
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Irizar, Agurtzan ...
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show more...
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Holt, Sylvester
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Thompson, Dawn
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Molin, Mikael, 1 ...
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Warringer, Jonas ...
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Liti, Gianni
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Medical Biotechn ...
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and Medical Biotechn ...
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Genetics
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Biochemistry and ...
- Articles in the publication
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Genome Research
- By the university
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Chalmers University of Technology
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University of Gothenburg