ArticleCell stress & chaperones2010
Hsp90 modulates CAG repeat instability in human cells.
Article in Cell stress & chaperones, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
25 citing papers in PubMed, 40 citations in OpenAlex.
- Hsp90: From Cellular to Organismal Proteostasis.Cells · 2022Review
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- A methylated lysine is a switch point for conformational communication in the chaperone Hsp90.Nature communications · 2020Article
- Heat-shock proteins: chaperoning DNA repair.Oncogene · 2020Review
- It's not magic - Hsp90 and its effects on genetic and epigenetic variation.Seminars in cell & developmental biology · 2019Review
- Review
- Genetic instability associated with loop or stem-loop structures within transcription units can be independent of nucleotide excision repair.Nucleic acids research · 2018Article
- Proteome Stability as a Key Factor of Genome Integrity.International journal of molecular sciences · 2017Review
- Stress-Induced Mutagenesis: Implications in Cancer and Drug Resistance.Annual review of cancer biology · 2017Article
- Network biology concepts in complex disease comorbidities.Nature reviews. Genetics · 2016Review
- Article
- Environmental stress induces trinucleotide repeat mutagenesis in human cells.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- The overdue promise of short tandem repeat variation for heritability.Trends in genetics : TIG · 2014Review
- Convergent transcription through microsatellite repeat tracts induces cell death.Molecular biology reports · 2014Article
- Targeting DNA repair pathways for cancer treatment: what's new?Future oncology (London, England) · 2014Review
- Article
- Cryptic variation in morphological evolution: HSP90 as a capacitor for loss of eyes in cavefish.Science (New York, N.Y.) · 2013Article
- A prescription for 'stress'--the role of Hsp90 in genome stability and cellular adaptation.Trends in cell biology · 2012Review
- Beyond junk-variable tandem repeats as facilitators of rapid evolution of regulatory and coding sequences.Genes · 2012Article
- Lessons from model organisms: phenotypic robustness and missing heritability in complex disease.PLoS genetics · 2012Article
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
The Hsp90 molecular chaperone has been implicated as a contributor to evolution in several organisms by revealing cryptic variation that can yield dramatic phenotypes when the chaperone is diverted from its normal functions by environmental stress. In addition, as a cancer drug target, Hsp90 inhibition has been documented to sensitize cells to DNA-damaging agents, suggesting a function for Hsp90 in DNA repair. Here we explore the potential role of Hsp90 in modulating the stability of nucleotide repeats, which in a number of species, including humans, exert subtle and quantitative consequences for protein function, morphological and behavioral traits, and disease. We report that impairment of Hsp90 in human cells induces contractions of CAG repeat tracks by tenfold. Inhibition of the recombinase Rad51, a downstream target of Hsp90, induces a comparable increase in repeat instability, suggesting that Hsp90-enabled homologous recombination normally functions to stabilize CAG repeat tracts. By contrast, Hsp90 inhibition does not increase the rate of gene-inactivating point mutations. The capacity of Hsp90 to modulate repeat-tract lengths suggests that the chaperone, in addition to exposing cryptic variation, might facilitate the expression of new phenotypes through induction of novel genetic variation.
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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.