Sylvie Doublié, Ph.D.

Professor

Training & Education

Dr. Doublié received her Ph.D. in Biochemistry and Biophysics from the University of North Carolina at Chapel Hill, studying the mechanism of aminoacyl-tRNA synthetases with Dr. Charlie Carter. She did postdoctoral work on proteins of the signal recognition particle with Dr. Stephen Cusack at the EMBL outstation in Grenoble, France and with Dr. Tom Ellenberger at Harvard Medical School, where she studied DNA polymerase mechanism. She joined the Department of Microbiology and Molecular Genetics in 1998.

Research Interests

Modifications to DNA, 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 enzymes and proteins that either generate or recognize them.

DNA polymerases, which faithfully replicate DNA, stumble when they encounter oxidized DNA lesions. These enzymes will either stall at the site of lesion or bypass it, initiating translesion synthesis. Uncovering the fundamental mechanisms underpinning lesion bypass is paramount to understand the initial events of mutagenesis. Our work focuses of human DNA polymerases, including polymerases beta and theta, which function in base excision repair and double strand break repair, respectively. Funded by NCI R01 CA52040 and CA080830.

Several DNA repair processes are in place to minimize damage in DNA. One of these processes is called base excision repair (BER). The first step in BER is carried out by DNA glycosylases, enzymes that locate and excise damaged base lesions. Our goal is to delineate the structural features of human DNA glycosylases that are involved in the recognition of DNA base damage induced by ionizing radiation. Our focus is on glycosylases that repair oxidized bases: the Nei-like enzymes (NEIL1-3), and NTHL1 glycosylase. This work is part of a program project grant funded by NCI (P01 CA098993). Additional funding from the Trunk Foundation is gratefully acknowledged.

Featured Publications

Prakash, A., Moharana, K., Wallace S.S., and Doublié S. (2017) Destabilization of the PCNA Trimer Mediated by its Interaction with the NEIL1 DNA Glycosylase Nucleic Acids Research Nucleic Acids Research 45:2897-2909, PMCID: PMC5389659

Wood R.D. and Doublié S. (2016) DNA polymerase θ (POLQ), double-strand break repair, and cancer DNA Repair 44:22-32 PMCID: PMC5114520

Zahn K.E., Averill M.A., Aller P. Wood R.D. and Doublié S. (2015) Human DNA polymerase θ grasps the primer terminus to mediate DNA repair Nat Struct Mol Biol 22:304-311 PMCID: PMC4385486

Liu M, Imamura K., Averill A. M., Wallace SS. and Doublié S*. (2013) Structural Characterization of a Mouse Ortholog of Human NEIL3 with a Marked Preference for Single-Stranded DNA. Structure 21:247-256. PMCID: PMC3856655

Yang Q, Gilmartin GM, Doublié S. (2010) Structural basis of UGUA recognition by the Nudix protein CFI(m)25 and implications for a regulatory role in mRNA 3' processing. PNAS 107:10062-7. PMCID PMC2890493

 

All Doublié publications

Sylvie Doublié, PhD, Headshot in lab

Contact Information

Office: E314A Given

Phone: 802-656-9531

Email

Lab Team

Vy Cao, Research Technician
Brittany Carroll, Graduate Student
Brian E. Eckenroth, Research Specialist
Amanda Nattress, Undergraduate Student
Scott Vanson, Graduate Student