ArticleMolecular and cellular biology2002
Mutations in DNA replication genes reduce yeast life span.
Article in Molecular and cellular biology, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 66 citations in OpenAlex.
- Aging, longevity, and the role of environmental stressors: a focus on wildfire smoke and air quality.Frontiers in toxicology · 2023Review
- Insights into the Conserved Regulatory Mechanisms of Human and Yeast Aging.Biomolecules · 2020Review
- Multiple roles of DNA2 nuclease/helicase in DNA metabolism, genome stability and human diseases.Nucleic acids research · 2020Review
- Transcription-induced formation of extrachromosomal DNA during yeast ageing.PLoS biology · 2019Article
- A Critical Role for Dna2 at Unwound Telomeres.Genetics · 2018Article
- Genomic Instabilities, Cellular Senescence, and Aging:Frontiers in medicine · 2018Review
- Extra View: Sirt1 Acts As A Gatekeeper Of Replication Initiation To Preserve Genomic Stability.Nucleus (Austin, Tex.) · 2018Review
- Article
- Evidence for the hallmarks of human aging in replicatively aging yeast.Microbial cell (Graz, Austria) · 2016Review
- Links between nucleolar activity, rDNA stability, aneuploidy and chronological aging in the yeast Saccharomyces cerevisiae.Biogerontology · 2014Article
- Rad52/Rad59-dependent recombination as a means to rectify faulty Okazaki fragment processing.The Journal of biological chemistry · 2014Article
- The role of DNA exonucleases in protecting genome stability and their impact on ageing.Age (Dordrecht, Netherlands) · 2012Review
- Premature aging with impaired oxidative stress defense in mice lacking TR4.American journal of physiology. Endocrinology and metabolism · 2011Article
- Article
- Genomic instability is associated with natural life span variation in Saccharomyces cerevisiae.PloS one · 2008Article
- Inferring transcriptional compensation interactions in yeast via stepwise structure equation modeling.BMC bioinformatics · 2008Article
- Article
- DNA replication stress, genome instability and aging.Nucleic acids research · 2007Review
- A network of multi-tasking proteins at the DNA replication fork preserves genome stability.PLoS genetics · 2005Article
- The transcriptome of prematurely aging yeast cells is similar to that of telomerase-deficient cells.Molecular biology of the cell · 2004Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Surprisingly, the contribution of defects in DNA replication to the determination of yeast life span has never been directly investigated. We show that a replicative yeast helicase/nuclease, encoded by DNA2 and a member of the same helicase subfamily as the RecQ helicases, is required for normal life span. All of the phenotypes of old wild-type cells, for example, extended cell cycle time, age-related transcriptional silencing defects, and nucleolar reorganization, occur after fewer generations in dna2 mutants than in the wild type. In addition, the life span of dna2 mutants is extended by expression of an additional copy of SIR2 or by deletion of FOB1, which also increase wild-type life span. The ribosomal DNA locus and the nucleolus seem to be particularly sensitive to defects in dna2 mutants, although in dna2 mutants extrachromosomal ribosomal circles do not accumulate during the aging of a mother cell. Several other replication mutations, such as rad27 Delta, encoding the FEN-1 nuclease involved in several aspects of genomic stability, also show premature aging. We propose that replication fork failure due to spontaneous, endogenous DNA damage and attendant genomic instability may contribute to replicative senescence. This may imply that the genomic instability, segmental premature aging symptoms, and cancer predisposition associated with the human RecQ helicase diseases, such as Werner, Bloom, and Rothmund-Thomson syndromes, are also related to replicative stress.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.