University of Vermont

College of Medicine

Department of Pathology and Laboratory Medicine


Sylvie Doublié, PhD

Department of Microbiology and Molecular Genetics

X-ray Crystallography of Protein/Nucleic Acid Complexes

Modifications in DNA or RNA, as part of normal cellular processes or as aberrations, can have profound biological consequences. The major thrust of my research program is to study these nucleic acid modifications in the context of the enzymes and proteins that generate and recognize them. Modifications in the DNA genome are caused by ionizing radiation, UV light, chemicals, etc. These DNA lesions can have profound consequences: DNA polymerases, which otherwise faithfully replicate DNA, often stumble when they encounter oxidative DNA lesions. Polymerases either will be blocked at the site of lesion, or bypass it. The latter case, referred to as translesion synthesis, may initiate an oncogenic process if the wrong base is inserted opposite the lesion. Uncovering the fundamental mechanisms underpinning translesion synthesis is paramount to understand the initial events of mutagenesis. Dr. Doublíe’s laboratory uses crystallographic and biochemical techniques to study at the atomic level the factors that influence the interactions between a replicative polymerase and DNA lesions. Our goal is to answer the following questions: How does a DNA polymerase sense the presence of a DNA lesion? What role does sequence context play in translesion synthesis? What triggers the transfer of DNA to the editing site in the event of a base mispair?


  1. Coseno ME, Martin G, Gilmartin G, Keller W, Doublié S: Crystal Structure of the 25 kDa Subunit of Human Cleavage Factor Im. Nucleic Acids Res 36:3474-3483, 2008 PMCID: PMC2425470
  2. Imamura K, Wallace SS, and Doublié S: Structural characterization of a viral NEIL1 ortholog unliganded and bound to abasic site-containing DNA. J Biol Chem 284:26174-26183, 2009 PMCID: PMC2758016
  3. Faucher F, Duclos S, Bandaru V, Wallace SS, and Doublié S: Crystal structures of two archaeal 8-oxoguanine DNA glycosylases provide structural insight into guanine/8-oxoguanine distinction. Structure 17:703-712, 2009 PMCID: PMC2758660
  4. Yang Q, Gilmartin GM, and Doublié S: Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing. Proc Natl Acad Sci U S A 107:10062-10067, 2010 PMCID: PMC2890493
  5. Hyde S, Eckenroth B, Smith B, Eberley W, Heintz N, Jackman J, and Doublié S: THG1, a unique 3'-5' nucleotidyltransferase, shares unexpected structural homology with canonical 5'-3' DNA polymerases. Proc Natl Acad Sci U S A 107:20305-20310, 2010 PMCID: PMC2996709

Last modified January 09 2012 04:33 PM