Research Topics
Genomes and Genes | SYLVIE DOUBLIESummaryAffiliation: University of Vermont Country: USA Publications
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Publications
The crystal structure of human endonuclease VIII-like 1 (NEIL1) reveals a zincless finger motif required for glycosylase activitySYLVIE DOUBLIE
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
Proc Natl Acad Sci U S A 101:10284-9. 2004..This "zincless finger" appears to be required for NEIL1 activity, because mutating a very highly conserved arginine within this motif greatly reduces the glycosylase activity of the enzyme...- The C-terminal lysine of Ogg2 DNA glycosylases is a major molecular determinant for guanine/8-oxoguanine distinctionFrédérick Faucher
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
J Mol Biol 397:46-56. 2010..Furthermore, this work provides a structural rationale for the lack of opposite base specificity in this family of enzymes... - Structural basis for the lack of opposite base specificity of Clostridium acetobutylicum 8-oxoguanine DNA glycosylaseFrédérick Faucher
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
DNA Repair (Amst) 8:1283-9. 2009..A structural comparison with human OGG1 provides a rationale for the lack of opposite base specificity displayed by the bacterial Ogg... 
Structural and biochemical investigation of the role in proofreading of a beta hairpin loop found in the exonuclease domain of a replicative DNA polymerase of the B familyMatthew Hogg
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 282:1432-44. 2007....- Crystal structure of a replicative DNA polymerase bound to the oxidized guanine lesion guanidinohydantoinPierre Aller
Department of Microbiology and Molecular Genetics, Stafford Hall, University of Vermont, Burlington, Vermont 05405, USA
Biochemistry 49:2502-9. 2010.... - The miscoding potential of 5-hydroxycytosine arises due to template instability in the replicative polymerase active siteKarl E Zahn
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, United States
Biochemistry 50:10350-8. 2011..Taken together, these data imply that the nonuniform templating by 5-OHC is due to weakened stacking capabilities, which allows dAMP incorporation to proceed in a manner similar to that observed opposite abasic sites... - A structural rationale for stalling of a replicative DNA polymerase at the most common oxidative thymine lesion, thymine glycolPierre Aller
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, 95 Carrigan Drive, Burlington, VT 05405, USA
Proc Natl Acad Sci U S A 104:814-8. 2007.... - Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processingQin Yang
Department of Microbiology and Molecular Genetics, Stafford Hall, University of Vermont, Burlington, VT 05405, USA
Proc Natl Acad Sci U S A 107:10062-7. 2010..Furthermore, the mutually exclusive binding of RNA and the signaling molecule Ap(4)A (diadenosine tetraphosphate) by CFI(m)25 suggests a potential role for small molecules in the regulation of mRNA 3' processing... - Crystal structure of a human cleavage factor CFI(m)25/CFI(m)68/RNA complex provides an insight into poly(A) site recognition and RNA loopingQin Yang
Department of Microbiology and Molecular Genetics, University of Vermont, Stafford Hall, Burlington, VT 05405, USA
Structure 19:368-77. 2011..The intrinsic ability of CFI(m) to direct RNA looping may provide a mechanism for its function in the regulation of alternative poly(A) site selection... - Structural and biochemical studies of a plant formamidopyrimidine-DNA glycosylase reveal why eukaryotic Fpg glycosylases do not excise 8-oxoguanineStéphanie Duclos
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, Burlington, VT 05405 0068, USA
DNA Repair (Amst) 11:714-25. 2012..Although the exact role of the loop remains to be further explored, it is now clear that this protein segment is specific to the processing of 8-oxoG... - Structural characterization of viral ortholog of human DNA glycosylase NEIL1 bound to thymine glycol or 5-hydroxyuracil-containing DNAKayo Imamura
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 287:4288-98. 2012..This finding suggests that lesion recognition by Nei occurs before the damaged base flips into the glycosylase active site... - Caught bending the A-rule: crystal structures of translesion DNA synthesis with a non-natural nucleotideKarl E Zahn
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA
Biochemistry 46:10551-61. 2007.... - Overproduction, crystallization and preliminary crystallographic analysis of a novel human DNA-repair enzyme that recognizes oxidative DNA damageViswanath Bandaru
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, The University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
Acta Crystallogr D Biol Crystallogr 60:1142-4. 2004..The unliganded NEIL1 crystallizes in space group R3, with unit-cell parameters a = b = 132.2, c = 51.1 A. Complete data sets were collected from native, selenomethionyl and iodinated NEIL1 to 2.1, 2.3 and 2.4 angstroms, respectively... - Infidelity out in the openSYLVIE DOUBLIE
Department of Microbiology and Molecular Genetics, The University of Vermont, Burlington, VT 05405, USA
Structure 12:1749-50. 2004..this issue of Structure). The N-domain of the polymerase, which is closed when the correct nucleotide pairs with the template base, adopts a partially open conformation suboptimal for catalysis... - Structural characterization of Clostridium acetobutylicum 8-oxoguanine DNA glycosylase in its apo form and in complex with 8-oxodeoxyguanosineFrédérick Faucher
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
J Mol Biol 387:669-79. 2009..A structural comparison of CacOgg with human OGG1, in complex with 8-oxoG containing DNA, provides a structural rationale for the lack of opposite base specificity displayed by CacOgg... - A crystallographic study of the role of sequence context in thymine glycol bypass by a replicative DNA polymerase serendipitously sheds light on the exonuclease complexPierre Aller
Department of Microbiology andMolecular Genetics, Stafford Hall, University of Vermont, Burlington, VT 05405, USA
J Mol Biol 412:22-34. 2011.... - Kinetics of mismatch formation opposite lesions by the replicative DNA polymerase from bacteriophage RB69Matthew Hogg
Department of Microbiology and Molecular Genetics, 95 Carrigan Drive, University of Vermont, Burlington, Vermont 05405, USA
Biochemistry 49:2317-25. 2010..We have also solved the crystal structure of the L561A variant forming an 8-oxoG.dATP mispair and show that the propensity for forming this mispair depends on an enlarged polymerase active site... - Purification, crystallization and preliminary X-ray diffraction of a disulfide cross-linked complex between bovine poly(A) polymerase and a chemically modified 15-mer oligo(A) RNAQin Yang
Department of Microbiology and Molecular Genetics, Stafford Hall, University of Vermont, Burlington, Vermont 05405, USA
Acta Crystallogr Sect F Struct Biol Cryst Commun 67:241-4. 2011..The crystals, which belonged to space group P2 and harbored two protein-RNA complexes per asymmetric unit, diffracted X-rays to 2.25 Å resolution... - DNA polymerases provide a canon of strategies for translesion synthesis past oxidatively generated lesionsKarl E Zahn
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT 05405, USA
Curr Opin Struct Biol 21:358-69. 2011.... - Lesion bypass activity of DNA polymerase θ (POLQ) is an intrinsic property of the pol domain and depends on unique sequence insertsMatthew Hogg
Department of Microbiology and Molecular Genetics, University of Vermont, 95 Carrigan Drive, Burlington, VT 05405, USA
J Mol Biol 405:642-52. 2011..However, removal of insertions 2 and 3 reduces activity on undamaged DNA and completely abrogates the ability of the enzyme to bypass abasic sites or thymine glycol lesions... - The structure of human cleavage factor I(m) hints at functions beyond UGUA-specific RNA binding: a role in alternative polyadenylation and a potential link to 5' capping and splicingQin Yang
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, VT, USA
RNA Biol 8:748-53. 2011.... - Structural characterization of a viral NEIL1 ortholog unliganded and bound to abasic site-containing DNAKayo Imamura
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405 0068, USA
J Biol Chem 284:26174-83. 2009..In the MvNei1.tetrahydrofuran complex a tyrosine located at the tip of the putative lesion recognition loop stacks against the furan ring; the tyrosine is predicted to adopt a different conformation to accommodate a modified base... - The soul of a new structure-function machineSYLVIE DOUBLIE
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, VT 05405, USA
Structure 16:3-4. 2008 - Phosphonoformic acid inhibits viral replication by trapping the closed form of the DNA polymeraseKarl E Zahn
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 286:25246-55. 2011..The closed state of the fingers domain traps the variant polymerase in the untranslocated state and increases affinity for PFA. This finding provides a model for the mechanism of UL54 stalling by PFA... - Structural biology of poly(A) site definitionQin Yang
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, USA
Wiley Interdiscip Rev RNA 2:732-47. 2011..WIREs RNA 2011 2 732-747 DOI: 10.1002/wrna.88 For further resources related to this article, please visit the WIREs website... - Crystal structures of two archaeal 8-oxoguanine DNA glycosylases provide structural insight into guanine/8-oxoguanine distinctionFrédérick Faucher
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, Burlington, VT 05405 0068, USA
Structure 17:703-12. 2009..This prediction was substantiated by measuring the glycosylase/lyase activity of a C-terminal deletion mutant of MjaOgg... - Crystal structure of the 25 kDa subunit of human cleavage factor ImMolly Coseno
Department of Microbiology and Department of Molecular Genetics, University of Vermont, Burlington, VT 05405, USA
Nucleic Acids Res 36:3474-83. 2008.... 
Structural characterization of a mouse ortholog of human NEIL3 with a marked preference for single-stranded DNAMinmin Liu
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Stafford Hall, 95 Carrigan Drive, Burlington, VT 05405 0068, USA
Structure 21:247-56. 2013..These structural features provide insight into the substrate specificity and marked preference of Neil3 for ssDNA...- Structural and functional analysis of the CspB protease required for Clostridium spore germinationChloe M Adams
Graduate Program in Cell, Molecular and Biomedical Sciences, University of Vermont, Burlington, Vermont, United States of America
PLoS Pathog 9:e1003165. 2013..difficile. Collectively, our study provides the first molecular insight into CspB activity and function. These studies may inform the development of inhibitors that can prevent clostridial spore germination and thus disease transmission... - The Fpg/Nei family of DNA glycosylases: substrates, structures, and search for damageAishwarya Prakash
Department of Microbiology and Molecular Genetics, The Markey Center for Molecular Genetics, University of Vermont, Burlington, Vermont, USA
Prog Mol Biol Transl Sci 110:71-91. 2012..This review summarizes the current structural knowledge of the Fpg/Nei family members, emphasizes their substrate specificities, and describes how these enzymes search for lesions... - tRNA(His) guanylyltransferase (THG1), a unique 3'-5' nucleotidyl transferase, shares unexpected structural homology with canonical 5'-3' DNA polymerasesSamantha J Hyde
Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont 05405, USA
Proc Natl Acad Sci U S A 107:20305-10. 2010..The ability of the same structural architecture to catalyze both 5'-3' and 3'-5' reactions raises important questions concerning selection of the 5'-3' mechanism during the evolution of nucleotide polymerases... - Crystallographic software: a sustainable resource for the communityStephen J Everse
Department of Biochemistry, University of Vermont, Burlington, VT, USA
Methods Mol Biol 364:273-8. 2007..Links to download the programs, available tutorials, and references to cite when using the program/site are also provided... - Activation of the hetero-octameric ATP phosphoribosyl transferase through subunit interface rearrangement by a tRNA synthetase paralogKaren S Champagne
Department of Microbiology and Molecular Genetics and Biochemistry, University of Vermont, Burlington, Vermont 05405, USA
J Biol Chem 280:34096-104. 2005.... - Crystallographic snapshots of a replicative DNA polymerase encountering an abasic siteMatthew Hogg
Department of Microbiology and Molecular Genetics, Markey Center for Molecular Genetics, University of Vermont, Burlington, VT, USA
EMBO J 23:1483-93. 2004..The polymerase incorporates dAMP across the lesion under crystallization conditions, indicating that the different conformations observed in the crystal may be part of the active site switching reaction pathway...
Research Grants
- CRYSTALLOGRAPHIC STUDIES OF EUKARYOTIC POLY(A)POLYMERASESYLVIE DOUBLIE; Fiscal Year: 2006..It is expected that these results will not only provide a sound structural basis for understanding the mechanism of polyadenylation at the molecular level but will also shed light on the mechanisms of processivity and repression. ..
- Processing of Radiation Damage by Translesion DNA SynthesisSYLVIE DOUBLIE; Fiscal Year: 2010..This research bears directly on public health since it addresses the fundamental mechanisms underpinning cell killing and mutagenesis by therapeutic levels of ionizing radiation. ..