ArticleMolecular and cellular biology2004
Saccharomyces cerevisiae Srs2 DNA helicase selectively blocks expansions of trinucleotide repeats.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed, 80 citations in OpenAlex.
- Massive contractions of myotonic dystrophy type 2-associated CCTG tetranucleotide repeats occur via double-strand break repair with distinct requirements for DNA helicases.G3 (Bethesda, Md.) · 2024Article
- The separation pin distinguishes the pro- and anti-recombinogenic functions of Saccharomyces cerevisiae Srs2.Nature communications · 2023Article
- Modifiers of CAG/CTG Repeat Instability: Insights from Mammalian Models.Journal of Huntington's disease · 2021Review
- On the wrong DNA track: Molecular mechanisms of repeat-mediated genome instability.The Journal of biological chemistry · 2020Review
- Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.Trends in genetics : TIG · 2018Review
- Break-induced replication promotes formation of lethal joint molecules dissolved by Srs2.Nature communications · 2017Article
- Review
- Replication stalling and DNA microsatellite instability.Biophysical chemistry · 2017Review
- Differential requirement of Srs2 helicase and Rad51 displacement activities in replication of hairpin-forming CAG/CTG repeats.Nucleic acids research · 2017Article
- Multifunctional roles of Saccharomyces cerevisiae Srs2 protein in replication, recombination and repair.FEMS yeast research · 2017Review
- Break-induced replication: an unhealthy choice for stress relief?Nature structural & molecular biology · 2017Article
- The role of break-induced replication in large-scale expansions of (CAG)Nature structural & molecular biology · 2017Article
- Expansion of Interstitial Telomeric Sequences in Yeast.Cell reports · 2015Article
- Molecular mechanism of resolving trinucleotide repeat hairpin by helicases.Structure (London, England : 1993) · 2015Article
- Article
- RTEL1 inhibits trinucleotide repeat expansions and fragility.Cell reports · 2014Article
- Highly specific contractions of a single CAG/CTG trinucleotide repeat by TALEN in yeast.PloS one · 2014Article
- The balancing act of DNA repeat expansions.Current opinion in genetics & development · 2013Review
- Genome-wide screen reveals replication pathway for quasi-palindrome fragility dependent on homologous recombination.PLoS genetics · 2013Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Trinucleotide repeats (TNRs) undergo frequent mutations in families afflicted with certain neurodegenerative disorders and in model organisms. TNR instability is modulated both by the repeat tract itself and by cellular proteins. Here we identified the Saccharomyces cerevisiae DNA helicase Srs2 as a potent and selective inhibitor of expansions. srs2 mutants had up to 40-fold increased expansion rates of CTG, CAG, and CGG repeats. The expansion phenotype was specific, as mutation rates at dinucleotide repeats, at unique sequences, or for TNR contractions in srs2 mutants were not altered. Srs2 is known to suppress inappropriate genetic recombination; however, the TNR expansion phenotype of srs2 mutants was largely independent of RAD51 and RAD52. Instead, Srs2 mainly functioned with DNA polymerase delta to block expansions. The helicase activity of Srs2 was important, because a point mutant lacking ATPase function was defective in blocking expansions. Purified Srs2 was substantially better than bacterial UvrD helicase at in vitro unwinding of a DNA substrate that mimicked a TNR hairpin. Disruption of the related helicase gene SGS1 did not lead to excess expansions, nor did wild-type SGS1 suppress the expansion phenotype of an srs2 strain. We conclude that Srs2 selectively blocks triplet repeat expansions through its helicase activity and primarily in conjunction with polymerase delta.
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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.