Department of Microbiology and Molecular Genetics

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

Rohlfing AE, Eckenroth BE, Forster ER, Kevorkian Y, Donnelly ML, Benito de la Puebla H, Doublié S, Shen A. (2019) The CspC pseudoprotease regulates germination of Clostridioides difficile spores in response to multiple environmental signals. PLoS Genetics 15:e1008224. PMCID: PMC6636752

Huang J, Alnajjar KS, Mahmoud MM, Eckenroth BE, Doublié S, Sweasy J. (2018) The nature of the DNA substrate influences pre-catalytic conformational changes of DNA polymerase β. J. Biol. Chem. 293:15084-15094 PMCID: PMC6166726 

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

All Doublié publications