# Tom Ellenberger
Tom Ellenberger (also published as T. Ellenberger and Tom E. Ellenberger) is a structural biologist and professor of biochemistry and molecular biophysics at [Washington University in St. Louis](https://www.edgepedia.org/washington-university-in-st-louis), known for crystal structures of [DNA repair](https://www.edgepedia.org/dna-repair) glycosylases, the bacteriophage T7 replication machinery, and site-specific recombinases.[1](https://biochem.wustl.edu/faculty/ellenberger) • [2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) His laboratory studies the molecular structures and cellular functions of proteins that replicate DNA, repair chemical damage, and regulate chromatin structure.[1](https://biochem.wustl.edu/faculty/ellenberger)
| Fact | Detail |
|---|---|
| Field | Structural biology of DNA replication, repair, and recombination proteins[1](https://biochem.wustl.edu/faculty/ellenberger) |
| Current role | Professor of Biochemistry and Molecular Biophysics, Washington University in St. Louis[1](https://biochem.wustl.edu/faculty/ellenberger) |
| Department head | Raymond H. Wittcoff Professor and head of Biochemistry and Molecular Biophysics, effective January 1, 2006[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) |
| Training | D.V.M., Iowa State University; Ph.D. in pharmacology, Harvard Medical School, 1989, with Stephen M. Beverley[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) |
| Signature work | 2.2 Å structure of the T7 DNA polymerase replication complex (Nature, 1998); human AAG glycosylase bound to DNA (Cell, 1998)[3](https://rcsb.org/structure/1T7P) • [4](http://www.cell.com/article/S0092867400817559/pdf) |
## Education and training
Ellenberger earned a doctorate in veterinary medicine from [Iowa State University](https://www.edgepedia.org/iowa-state-university)'s College of Veterinary Medicine before his graduate studies, where he developed an interest in pharmacology and medicine.[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) He then earned a Ph.D. in pharmacology from Harvard Medical School in 1989, studying with [Stephen M. Beverley](https://www.edgepedia.org/stephen-beverley).[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) His doctoral work examined the genetic mechanisms of acquired drug resistance in *Leishmania major*, a parasite that infects approximately 12 million people worldwide.[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/)
## Career record
According to *The Source*, a Washington University publication, Ellenberger spent twelve years at Harvard Medical School, where he held the Hsien Wu and Daisy Yen Wu Professorship of Biological Chemistry and Molecular Pharmacology.[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) In December 2005 Washington University announced his appointment as the Raymond H. Wittcoff Professor and head of the Department of Biochemistry and Molecular Biophysics, effective January 1, 2006.[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/) He remains a professor in that department.[1](https://biochem.wustl.edu/faculty/ellenberger) During his Harvard years he co-authored the second edition of the textbook *DNA Repair and Mutagenesis*.[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/)
## Representative work
His 1998 Nature paper reported a 2.2 Å crystal structure of the replicative [DNA polymerase](https://www.edgepedia.org/dna-polymerase) from bacteriophage T7 complexed with a DNA primer-template, a nucleoside triphosphate, and its processivity factor, E. coli thioredoxin (PDB entry 1T7P).[3](https://rcsb.org/structure/1T7P) • [8](https://arep.med.harvard.edu/biophysics/faculty/Ellenberger96.html) The structure showed a conformational change in the polymerase that engages conserved residues and two metals with the DNA and nucleotide substrates, promoting incorporation of the correct template-specified nucleotide.[8](https://arep.med.harvard.edu/biophysics/faculty/Ellenberger96.html)
In the 1996 Cell paper *Structural basis for the excision repair of alkylation-damaged DNA* (Cell 86, 321–329, July 26, 1996), his group reported the 1.8 Å crystal structure of the E. coli monofunctional DNA glycosylase AlkA, revealing a large hydrophobic cleft unusually rich in aromatic residues, with an aspartate projecting into the cleft that is essential for catalysis.[9](https://profiles.wustl.edu/en/publications/structural-basis-for-the-excision-repair-of-alkylation-damaged-dn/)
The 1998 Cell paper on human 3-methyladenine DNA glycosylase (AAG) complexed to a mechanism-based pyrrolidine inhibitor reported a 2.7 Å structure in which the enzyme intercalates into the minor groove of DNA, flipping the abasic pyrrolidine nucleotide into the active site, where a bound water is poised for nucleophilic attack; a tyrosine, later identified as Tyr162, inserts into the minor groove as a surrogate base that stabilizes the DNA distortion.[4](http://www.cell.com/article/S0092867400817559/pdf) • [10](https://www.sciencedirect.com/science/article/abs/pii/S0921877700000276) The geometry is consistent with direct, in-line displacement of damaged bases from DNA.[4](http://www.cell.com/article/S0092867400817559/pdf)
His group also determined the 1.9 Å crystal structure of the lambda integrase catalytic domain, showing the attacking Tyr342 nucleophile on a flexible loop about 20 Å from a basic groove containing the other catalytically essential residues, a bipartite active site that accounts for both cis and trans cleavage of DNA by integrase-family recombinases.[11](https://profiles.wustl.edu/en/publications/flexibility-in-dna-recombination-structure-of-the-lambda-integras/)
## Research program
At Washington University the laboratory has extended the replication and repair work. A 2015 *Nucleic Acids Research* paper showed that human DNA ligase III bridges two DNA ends to promote specific intermolecular DNA end joining.[1](https://biochem.wustl.edu/faculty/ellenberger) A 2013 *Biochemistry* paper showed that discrete interactions between the T7 primase-helicase and DNA polymerase drive formation of a priming complex containing two copies of DNA polymerase.[1](https://biochem.wustl.edu/faculty/ellenberger) PDB records list his group's 2016 deposit of the T7 replisome in the absence of DNA, at 4.802 Å, cited to a 2017 *Structure* paper on flexibly linked DNA polymerases within the replisome.[12](https://pdbj.org/search/pdb-author?query=%22Ellenberger%2C+T.%22) The earlier primase-helicase work gave the field a structural framework for coupling: a 3.45 Å crystal structure of the T7 primase-helicase showed a heptamer with a crown-like shape and a double-jointed arrangement that permits free range of motion between the primase and helicase domains, suggesting how continuous unwinding at the replication fork can be periodically coupled to Okazaki fragment synthesis.[13](https://www.cell.com/molecular-cell/fulltext/S1097-2765(03)00442-8)
## Funding and honors
The National Institute of General Medical Sciences funded his program through several long-running R01 grants, R01-GM055390 (Crystallographic Studies of DNA Replication Proteins) and R01-GM059902 (Structural Studies of Site-Specific Recombination).[5](https://grantome.com/grant/NIH/R01-GM055390-10) • [6](https://grantome.com/grant/NIH/R01-GM059902-11) In March 2016 he received a five-year grant from the [National Cancer Institute](https://www.edgepedia.org/national-cancer-institute) for research on pharmacological modulation of poly([ADP-ribose](https://www.edgepedia.org/adp-ribose)) metabolism.[7](https://biochem.wustl.edu/archives/category/resawards/resawards-ellenberger) Washington University's recruitment was supported by a $6 million grant from the Danforth Foundation, and Iowa State's College of Veterinary Medicine awarded him the Stange Award for Outstanding Professional Achievements.[2](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/)
## References
1. [Tom Ellenberger, D.V.M., Ph.D. – Department of Biochemistry and Molecular Biophysics, Washington University](https://biochem.wustl.edu/faculty/ellenberger)
2. [Ellenberger named head of biochemistry & molecular biophysics – The Source, Washington University](https://source.washu.edu/2005/12/ellenberger-named-head-of-biochemistry-molecular-biophysics/)
3. [RCSB PDB 1T7P: T7 DNA polymerase complexed to DNA primer/template, a nucleoside triphosphate, and thioredoxin](https://rcsb.org/structure/1T7P)
4. [Crystal Structure of a Human Alkylbase-DNA Repair Enzyme Complexed to DNA (Cell, 1998)](http://www.cell.com/article/S0092867400817559/pdf)
5. [Crystallographic Studies of DNA Replication Proteins – NIH R01-GM055390](https://grantome.com/grant/NIH/R01-GM055390-10)
6. [Structural Studies of Site-Specific Recombination – NIH R01-GM059902](https://grantome.com/grant/NIH/R01-GM059902-11)
7. [Ellenberger – Department of Biochemistry and Molecular Biophysics research awards](https://biochem.wustl.edu/archives/category/resawards/resawards-ellenberger)
8. [Tom Ellenberger – Harvard Biophysics faculty page](https://arep.med.harvard.edu/biophysics/faculty/Ellenberger96.html)
9. [Structural basis for the excision repair of alkylation-damaged DNA – WashU Research Profiles](https://profiles.wustl.edu/en/publications/structural-basis-for-the-excision-repair-of-alkylation-damaged-dn/)
10. [Structural studies of human alkyladenine glycosylase and E. coli 3-methyladenine glycosylase (review)](https://www.sciencedirect.com/science/article/abs/pii/S0921877700000276)
11. [Flexibility in DNA recombination: Structure of the lambda integrase catalytic core – WashU Research Profiles](https://profiles.wustl.edu/en/publications/flexibility-in-dna-recombination-structure-of-the-lambda-integras/)
12. [Search by PDB author 'Ellenberger, T.' – Protein Data Bank Japan](https://pdbj.org/search/pdb-author?query=%22Ellenberger%2C+T.%22)
13. https://www.cell.com/molecular-cell/fulltext/S1097-2765(03)00442-8
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*Topic: Encyclopedia › Life and health › Life and health scientists › Life scientists › Researchers in structural biology, biochemistry, and biophysics › Protein crystallography and structural genomics › Enzyme and nucleic acid machinery structures*
*Initially written Sep 21, 2026 · Reviewed: Sep 25, 2026 · Edited: Sep 25, 2026; Oct 11, 2026; Oct 15, 2026 · Last review: Sep 25, 2026*
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