ArticleNucleic acids research2013
A transient α-helical molecular recognition element in the disordered N-terminus of the Sgs1 helicase is critical for chromosome stability and binding of Top3/Rmi1.
Article in Nucleic acids research, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 23 citations in OpenAlex.
- A screen for synthetic genetic interactions with the Saccharomyces cerevisiae hrq1ΔN allele.G3 (Bethesda, Md.) · 2025Article
- Mechanism of Bloom syndrome complex assembly required for double Holliday junction dissolution and genome stability.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Full structural ensembles of intrinsically disordered proteins from unbiased molecular dynamics simulations.Communications biology · 2021Article
- The Bloom syndrome complex senses RPA-coated single-stranded DNA to restart stalled replication forks.Nature communications · 2021Article
- Review
- Disorder for Dummies: Functional Mutagenesis of Transient Helical Segments in Disordered Proteins.Methods in molecular biology (Clifton, N.J.) · 2020Article
- Generation of the configurational ensemble of an intrinsically disordered protein from unbiased molecular dynamics simulation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Competing interaction partners modulate the activity of Sgs1 helicase during DNA end resection.The EMBO journal · 2019Article
- High-throughput creation and functional profiling of DNA sequence variant libraries using CRISPR-Cas9 in yeast.Nature biotechnology · 2018Article
- Article
- Genetic Separation of Sae2 Nuclease Activity from Mre11 Nuclease Functions in Budding Yeast.Molecular and cellular biology · 2017Article
- A Novel Rrm3 Function in Restricting DNA Replication via an Orc5-Binding Domain Is Genetically Separable from Rrm3 Function as an ATPase/Helicase in Facilitating Fork Progression.PLoS genetics · 2016Article
- Effects of Linker Length and Transient Secondary Structure Elements in the Intrinsically Disordered Notch RAM Region on Notch Signaling.Journal of molecular biology · 2015Article
- Digested disorder, Quarterly intrinsic disorder digest (October-November-December, 2013).Intrinsically disordered proteins · 2015Article
- Structural Motifs Critical for In Vivo Function and Stability of the RecQ-Mediated Genome Instability Protein Rmi1.PloS one · 2015Article
- Molecular mechanism of double Holliday junction dissolution.Cell & bioscience · 2014Review
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Authors and funding
3 authors at 2 institutions in 1 country.
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Abstract
The RecQ-like DNA helicase family is essential for the maintenance of genome stability in all organisms. Sgs1, a member of this family in Saccharomyces cerevisiae, regulates early and late steps of double-strand break repair by homologous recombination. Using nuclear magnetic resonance spectroscopy, we show that the N-terminal 125 residues of Sgs1 are disordered and contain a transient α-helix that extends from residue 25 to 38. Based on the residue-specific knowledge of transient secondary structure, we designed proline mutations to disrupt this α-helix and observed hypersensitivity to DNA damaging agents and increased frequency of genome rearrangements. In vitro binding assays show that the defects of the proline mutants are the result of impaired binding of Top3 and Rmi1 to Sgs1. Extending mutagenesis N-terminally revealed a second functionally critical region that spans residues 9-17. Depending on the position of the proline substitution in the helix functional impairment of Sgs1 function varied, gradually increasing from the C- to the N-terminus. The multiscale approach we used to interrogate structure/function relationships in the long disordered N-terminal segment of Sgs1 allowed us to precisely define a functionally critical region and should be generally applicable to other disordered proteins.
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