About

Tom Tullius is a professor conducting research in genomics, structural biology, and biophysical chemistry. He holds a faculty appointment in Chemistry and is also a Professor of Pharmacology and Experimental Therapeutics at the Boston University School of Medicine. His research group introduced hydroxyl radical footprinting, a widely used technique for studying the structure of DNA, DNA-protein complexes, and RNA. His work investigates the connection between the structural properties of DNA and genomics, including studies on DNA shape and its role in evolutionary selection, as well as mapping DNA and RNA structures at high resolution. Professor Tullius is an elected Fellow of the American Association for the Advancement of Science and serves on the Editorial Board of the open access journal PeerJ. He is the Director of the Boston University Bioinformatics Program. His research projects include developing methods to map DNA shape at single nucleotide resolution and exploring RNA tertiary structure transcriptome-wide. His work has contributed to understanding how DNA shape influences transcription factor binding and gene regulation, and his lab collaborates with NIH and other institutions to advance genomic and structural biology research.

Research topics

• Chemistry
• Biology
• Computational biology
• Genetics
• Stereochemistry

Selected publications

• Faculty Opinions recommendation of Molecular structure of a U•A-U-rich RNA triple helix with 11 consecutive base triples.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2020-04-09

  datasetOpen access1st authorCorresponding

  Three-dimensional structures have been solved for several naturally occurring RNA triple helices, although all are limited to six or fewer consecutive base triples, hindering accurate estimation of global and local structural parameters. We present an X-ray crystal structure of a right-handed, UA-U-rich RNA triple helix with 11 continuous base triples. Due to helical unwinding, the RNA triple helix spans an average of 12 base triples per turn. The double helix portion of the RNA triple helix is more similar to both the helical and base step structural parameters of A -RNA rather than A-RNA. Its most striking features are its wide and deep major groove, a smaller inclination angle and all three strands favoring a C3 -endo sugar pucker. Despite the presence of a third strand, the diameter of an RNA triple helix remains nearly identical to those of DNA and RNA double helices. Contrary to our previous modeling predictions, this structure demonstrates that an RNA triple helix is not limited in length to six consecutive base triples and that longer RNA triple helices may exist in nature. Our structure provides a starting point to establish structural parameters of the so-called 'ideal' RNA triple helix, analogous to A-RNA and B-DNA double helices.

  PublisherOA PDFDOI

• Faculty Opinions recommendation of The tardigrade damage suppressor protein binds to nucleosomes and protects DNA from hydroxyl radicals.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2019-11-30

  dataset1st authorCorresponding

  Tardigrades, also known as water bears, are animals that can survive extreme conditions.The tardigrade Ramazzottius varieornatus contains a unique nuclear protein termed Dsup, for damage suppressor, which can increase the resistance of human cells to DNA damage under conditions, such as ionizing radiation or hydrogen peroxide treatment, that generate hydroxyl radicals.Here we find that R. varieornatus Dsup is a nucleosome-binding protein that protects chromatin from hydroxyl radicals.Moreover, a Dsup ortholog from the tardigrade Hypsibius exemplaris similarly binds to nucleosomes and protects DNA from hydroxyl radicals.Strikingly, a conserved region in Dsup proteins exhibits sequence similarity to the nucleosomebinding domain of vertebrate HMGN proteins and is functionally important for nucleosome binding and hydroxyl radical protection.These findings suggest that Dsup promotes the survival of tardigrades under diverse conditions by a direct mechanism that involves binding to nucleosomes and protecting chromosomal DNA from hydroxyl radicals.

  PublisherDOI

• Faculty Opinions recommendation of Comparison of discriminative motif optimization using matrix and DNA shape-based models.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2018-03-21

  dataset1st authorCorresponding
  PublisherDOI

• Experimental maps of DNA structure at nucleotide resolution distinguish intrinsic from protein-induced DNA deformations

  Nucleic Acids Research · 2018-01-15 · 29 citations

  articleOpen accessSenior authorCorresponding

  Recognition of DNA by proteins depends on DNA sequence and structure. Often unanswered is whether the structure of naked DNA persists in a protein-DNA complex, or whether protein binding changes DNA shape. While X-ray structures of protein-DNA complexes are numerous, the structure of naked cognate DNA is seldom available experimentally. We present here an experimental and computational analysis pipeline that uses hydroxyl radical cleavage to map, at single-nucleotide resolution, DNA minor groove width, a recognition feature widely exploited by proteins. For 11 protein-DNA complexes, we compared experimental maps of naked DNA minor groove width with minor groove width measured from X-ray co-crystal structures. Seven sites had similar minor groove widths as naked DNA and when bound to protein. For four sites, part of the DNA in the complex had the same structure as naked DNA, and part changed structure upon protein binding. We compared the experimental map with minor groove patterns of DNA predicted by two computational approaches, DNAshape and ORChID2, and found good but not perfect concordance with both. This experimental approach will be useful in mapping structures of DNA sequences for which high-resolution structural data are unavailable. This approach allows probing of protein family-dependent readout mechanisms.

  PublisherOA PDFDOI

• Faculty Opinions recommendation of A unified approach for quantifying and interpreting DNA shape readout by transcription factors.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2018-03-21

  dataset1st authorCorresponding
  PublisherDOI

• Faculty Opinions recommendation of Intracellular nucleosomes constrain a DNA linking number difference of -1.26 that reconciles the Lk paradox.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2018-11-20

  dataset1st authorCorresponding
  PublisherDOI

• Faculty Opinions recommendation of Single-molecule decoding of combinatorially modified nucleosomes.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2016-05-27

  dataset1st authorCorresponding
  PublisherDOI

• Deuterated nucleotides as chemical probes of RNA structure: a detailed protocol for the enzymatic synthesis of a complete set of nucleotides specifically deuterated at ribose carbons

  ScienceOpen Research · 2015-01-01

  preprintOpen accessSenior authorCorresponding

  Abstract We describe here a detailed protocol for the synthesis of ribonucleotides specifically deuterated at each ribose carbon atom. We synthesized 20 specifically deuterated ribonucleotides: ATP, CTP, GTP, and UTP, each of which contained one of five deuterated riboses (either 1′-D, 2″-D, 3′-D, 4′-D, or 5′,5″-D 2 ). Our synthetic approach is inspired by the pioneering work of Tolbert and Williamson, who developed a method for the convenient one-pot enzymatic synthesis of nucleotides (Tolbert, T. J. and Williamson, J. R. (1996) J. Am. Chem. Soc. 118 , 7929–7940). Our protocol consists of a comprehensive list of required chemical and enzymatic reagents and equipment, detailed procedures for enzymatic assays and nucleotide synthesis, and chromatographic procedures for purification of deuterated nucleotides. As an example of the utility of specifically deuterated nucleotides, we used them to synthesize specifically deuterated sarcin/ricin loop (SRL) RNA and measured the deuterium kinetic isotope effect on hydroxyl radical cleavage of the SRL.

  PublisherOA PDFDOI

• 28 GBshape: a genome browser database for DNA shape annotations

  Journal of Biomolecular Structure and Dynamics · 2015-05-18 · 2 citations

  articleOpen access

  Many regulatory mechanisms require a high degree of specificity in protein-DNA binding. Nucleotide sequence does not provide an answer to the question of why a protein binds only to a small subset ...

  PublisherOA PDFDOI

• Faculty Opinions recommendation of Genome-wide nucleosome map and cytosine methylation levels of an ancient human genome.

  Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature · 2014-01-28

  dataset1st authorCorresponding
  PublisherDOI

Recent grants

• NIH Grant R01CA037444

  NIH · $252k · 1988

• NIH Grant R01GM041930

  NIH · $2.5M · 2005

• NIH Grant R01GM040894

  NIH · $2.4M · 2003

• NIH Grant R01HG003541

  NIH · $1.8M · 2012

• NIH Grant K04CA001208

  NIH · $295k · 1992

Frequent coauthors

• Mair E. A. Churchill

  Takeda (United States)

  50 shared

• Stephen C. J. Parker

  45 shared

• Neville R. Kallenbach

  35 shared

• Hsilin Ch'ng

  Columbia University

  25 shared

• Goran Bačić

  25 shared

• Richard L. Rubin

  George Washington University

  25 shared

• Jack D. Griffith

  University of North Carolina at Chapel Hill

  25 shared

• Jurek Dobrucki

  Jagiellonian University

  25 shared

Labs

• Tullius GroupPI

Education

• Ph.D., Chemistry

  Stanford University

  1979

• B.S., Chemistry

  UCLA

  1973

Awards & honors

• Fellow of the American Association for the Advancement of Sc…