An Age-Induced Switch to a Hyper-Recombinational State
Abstract
There is a strong correlation between age and cancer, but the mechanism by which this phenomenon occurs is unclear. We chose Saccharomyces cerevisiae to examine one of the hallmarks of cancer—genomic instability— as a function of cellular age. As diploid yeast mother cells aged, an ∼100-fold increase in loss of heterozygosity (LOH) occurred. Extending life-span altered neither the onset nor the frequency of age-induced LOH; the switch to hyper-LOH appears to be on its own clock. In young cells, LOH occurs by reciprocal recombination, whereas LOH in old cells was nonreciprocal, occurring predominantly in the old mother's progeny. Thus, nuclear genomes may be inherently unstable with age.
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In budding yeast, as the mother cell ages, there is a striking increase in genomic instability, as shown by marked loss of heterozygosity (LOH) in the daughter cell.
“as the mother yeast cell ages, there is a striking increase in genomic instability, as shown by marked loss of heterozygosity (LOH) in the daughter cell 26”
From The common biology of cancer and ageing (2007) · cites this paper as [26]
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References 24 · Cited by 208
- Authors
- McMurray, M. A., & Gottschling, D. E.
- Affiliations
- University of Washington (US)
- Corresponding author
- Gottschling, Daniel E.
- Venue
- Science
- Published
- 2003-09-26
- Volume
- 301
- Issue
- 5641
- Pages
- 1908-1911
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2089897141
- Cited by
- 208
- References
- 24
- Citations by year
- 2026: 1 · 2025: 2 · 2023: 2 · 2022: 1 · 2021: 2 · 2020: 6 · 2019: 8 · 2018: 6 · 2017: 7 · 2016: 13 · 2015: 9 · 2014: 17 · 2013: 15 · 2012: 6
- FWCI
- 4.00
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of General Medical Sciences (GM43893, R01GM043893)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Keywords
- cellular aging, genomic instability, loss of heterozygosity, reciprocal recombination, Saccharomyces cerevisiae, mother cell, lifespan extension, cancer susceptibility
- MeSH terms
- Aging, Cysteine Synthase, Diploidy, DNA Replication, DNA-Binding Proteins, DNA, Fungal, DNA, Ribosomal, Fungal Proteins, Genes, Fungal, Histone Deacetylases, Multienzyme Complexes, Mutation, Recombination, Genetic, Saccharomyces cerevisiae, Cellular Senescence, Gene Deletion, Loss of Heterozygosity, Saccharomyces cerevisiae Proteins, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Sirtuin 2
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