Tom Santangelo

Thomas SantangeloAssociate Professor
Office: 383 MRB
Phone: 970-491-3150
Education: Ph.D., Cornell University
Email: thomas.santangelo@colostate.edu
Research Title: Mechanisms and regulation of archaeal transcription

   

Archaeal metabolism, physiology, and molecular biology. 

      • Mechanisms of transcription regulation and RNA editing

Members of the Archaea often occupy unique, harsh, and ever-changing biological niches. These changing environments necessitate precise and timely regulation of gene expression. Our laboratory focuses on the regulation of transcription, from a global perspective to a detailed structure-function analysis of the archaeal RNA polymerase.

      • Mechanisms of DNA replication and repair

Some aspect of archaeal replication are novel to this Domain and the replicative strategies of archaeal species, particularly regarding replisome function and lagging strand DNA synthesis, remain poorly defined. We employ genetic and biochemical strategies to investigate the factors involved in DNA replication in vivo and vitro.

      •  Fermentative energy production systems and lipid metabolism

Thermococcus kodakarensis is reliant on a fermentative energy production pathway that either produces bio-hydrogen or reduces elemental sulfur. The electron flux associated with each pathway is under study using genetic and biochemical approaches. Rational metabolic-engineering efforts to generate strains with altered hydrogen production levels are also a focus of our research.

Selected Publications

Research Papers

29- Nalabothula, N., L. Xi, S. Bhattacharyya, J. Widom, J.P. Wang, J.N. Reeve, T.J. Santangelo, and Y.N. Fondufe-Mittendorf. 2013.  Archaeal nucleosome positioning in vivo and in vitro is directed by primary sequence motifs.  BMC Genomics. 14:391.

28- Pan, M., T.J. Santangelo, L. Cubonova, Z. Li, H. Metangmo, J. Ladner, J. Hurwitz, J.N. Reeve, and Z. Kelman. 2013. Thermococcus kodakarensis has two functional PCNA homologues but only one is essential for viability.  Extremophiles 17:453-61.

27- Cubonova, L., T. Richardson, B.W. Burkhart, Z. Kelman, B.A. Connolly, J.N. Reeve, and T.J. Santangelo. 2013. Archaeal DNA polymerase D but not DNA polymerase B is required for genome replication in Thermococcus kodakarensis.  J. Bacteriol. 195:2322-8.

26- Cubonova, L., M. Katano, T. Kanai, H. Atomi, J.N. Reeve, and T.J. Santangelo. 2012. An archaeal histone is required for transformation of Thermococcus kodakarensis. J. Bacteriol. 194:6864-74.

25- Hileman, T.H., and T.J. Santangelo. 2012. Genetic techniques for Thermococcus kodakarensis. Frontiers in Evolutionary and Genomic Microbiology 3:195.

24- Raina. M., S. Elgamal, T.J. Santangelo, and M. Ibba. 2012. Association of a multi-synthetase complex with translating ribosomes in the archaeon Thermococcus kodakarensis. FEBS Letters 586:2232-2238.

23- Pan, M., T.J. Santangelo, Z. Li, J.N. Reeve, and Z. Kelman. 2011. Thermococcus kodakarensis encodes three MCM homologs but only one is essential. Nucleic Acids Res. 39:9671-80.

22- Santangelo, T.J., L. Cubonova, and J.N. Reeve. 2011. Deletion of alternative pathways for reductantrecycling in Thermococcus kodakarensis increases hydrogen production. Mol Microbiol. 81:897-911.

21- Li, Z, M. Pan, T.J. Santangelo, W. Chemnitz, W. Yuan, J.L. Edwards, J. Hurwitz, J.N. Reeve, and Z. Kelman. 2011. A novel DNA nulcease is stimulated by association with the GINS complex. Nucleic Acids Res. 39:6114-23.

20- Li, Z.*, T.J. Santangelo*, Cubonova, L., J.N. Reeve and Z. Kelman. 2010. Affinity Purification of an Archaeal DNA Replication Protein Network. mBio 1:e00221-10. *Co-first authors

19- Santangelo, T.J. and J.N. Reeve. 2010. Deletion of Switch 3 results in an archaeal RNA polymerase that is defective in transcript elongation. J Biol Chem 285:23908-15.

18- Santangelo, T.J., L. Cubonova, and J.N. Reeve. 2010. Thermococcus kodakarensis genetics: TK1827-encoded beta-glycosidase, new positive-selection protocol, and targeted and repetitive deletion technology. Appl Environ Microbiol 76:1044-52

17- Santangelo, T.J., L. Cubonova, L., K.M. Skinner, and J.N. Reeve. 2009. Archaeal intrinsic termination in vivo. J Bacteriol 191:7102-8

16- Dev, K., T. J. Santangelo, S. Rothenburg, D. Neculai, M. Dey, F. Sicheri, T.E. Dever, J.N. Reeve, and A.G. Hinnebusch. 2009. Archaeal aIF2B interacts with eukaryotic translation initiation factors eIF2alpha and eIF2Balpha: Implications for aIF2B function and eIF2B regulation. J Mol Bio 392:701-22.

15- Hirata, A., T. Kanai, T. J. Santangelo, M. Tajiri, K. Manabe, J. N. Reeve, T. Imanaka, and K. S. Murakami. 2008. Archaeal RNA polymerase subunits E and F are not required for transcription in vitro, but a Thermococcus kodakarensis mutant lacking subunit F is temperature-sensitive. Mol Microbiol. 70:623-33.

14- Santangelo, T. J., L. Cubonova, and J. N. Reeve. 2008. Shuttle vector expression in Thermococcus kodakaraensis: contributions of cis elements to protein synthesis in a hyperthermophilic archaeon. Appl Environ Microbiol 74:3099-104.

13- Santangelo, T. J., L. Cubonova, R. Matsumi, H. Atomi, T. Imanaka, and J. N. Reeve. 2008. Polarity in archaeal operon transcription in Thermococcus kodakaraensis. J Bacteriol 190:2244-8.

12- Davydova, E. K., T. J. Santangelo, and L. B. Rothman-Denes. 2007. Bacteriophage N4 virion RNA polymerase interaction with its promoter DNA hairpin. Proc Natl Acad Sci U S A 104:7033-8.

11- Santangelo, T. J., L. Cubonova, C. L. James, and J. N. Reeve. 2007. TFB1 or TFB2 is sufficient for Thermococcus kodakaraensis viability and for basal transcription in vitro. J Mol Biol 367:344-57.

10- French, S. L., T. J. Santangelo, A. L. Beyer, and J. N. Reeve. 2007. Transcription and translation are coupled in Archaea. Mol Biol Evol 24:893-5.

9- Shin, J. H., T. J. Santangelo, Y. Xie, J. N. Reeve, and Z. Kelman. 2007. Archaeal minichromosome maintenance (MCM) helicase can unwind DNA bound by archaeal histones and transcription factors. J Biol Chem 282:4908-15.

8- Holmes, S. F., T. J. Santangelo, C. K. Cunningham, J. W. Roberts, and D. A. Erie. 2006. Kinetic investigation of Escherichia coli RNA polymerase mutants that influence nucleotide discrimination and transcription fidelity. J Biol Chem 281:18677-83.

7- Santangelo, T. J., and J. N. Reeve. 2006. Archaeal RNA polymerase is sensitive to intrinsic termination directed by transcribed and remote sequences. J Mol Biol 355:196-210.

6- Wickstrum, J. R.*, T. J. Santangelo*, and S. M. Egan. 2005. Cyclic AMP receptor protein and RhaR synergistically activate transcription from the L-rhamnose-responsive rhaSR promoter in Escherichia coli. J Bacteriol 187:6708-18. *Co-first authors

5- Shundrovsky, A., T. J. Santangelo, J. W. Roberts, and M. D. Wang. 2004. A single-molecule technique tostudy sequence-dependent transcription pausing. Biophys J 87:3945-53.

4- Santangelo, T. J., and J. W. Roberts. 2004. Forward translocation is the natural pathway of RNA release at an intrinsic terminator. Mol Cell 14:117-26.

3- Santangelo, T. J., and J. W. Roberts. 2003. Formation of long DNA templates containing site-specific alkane-disulfide DNA interstrand cross-links for use in transcription reactions. Methods Enzymol 371:120-32.

2- Santangelo, T. J., R. A. Mooney, R. Landick, and J. W. Roberts. 2003. RNA polymerase mutations that impair conversion to a termination-resistant complex by Q antiterminator proteins. Genes Dev 17:1281-92.

1- Adelman, K., A. La Porta, T. J. Santangelo, J. T. Lis, J. W. Roberts, and M. D. Wang. 2002. Single molecule analysis of RNA polymerase elongation reveals uniform kinetic behavior. Proc Natl Acad Sci U S A 99:13538-43.

Book Chapters

4- Santangelo, T.J. (2011) Transcription Termination. In: William J. Lennarz and M. Daniel Lane, Editor(s)- in-Chief, Encyclopedia of Biological Chemistry, Elsevier, New York

3- Santangelo, T.J. and J.N. Reeve. (2010) Genetic Tools and Manipulations of the Hyperthermophilic Heterotrophic Archaeon Thermococcus kodakarensis. In: Koki Horikoshi (ed.), Extremophiles Handbook, DOI 10.1007/978-4-431-53898-1_4.8, Springer Japan KK.

2- Shundrovsky, A., L. Bai, T.J. Santangelo, and M.D. Wang. (2008) Single Molecule Studies of RNA Polymerase Transcription. In A. Bock, R. Curtiss III, J.B. Kaper, F.C. Neidhardt, T. Nystrom, K.E. Rudd, and C.L. Squires (ed.), EcoSal - Escherichia coli and Salmonella: cellular and molecular Biology. [Online.] http://www.ecosal.org. ASM Press, Washington, D.C.

1- Santangelo T.J. and J.W. Roberts, Transcription Termination. In: William J. Lennarz and M. Daniel Lane, Editor(s)-in-Chief, Encyclopedia of Biological Chemistry, Elsevier, New York, 2004, Pages 195-199.

Reviews

4- Farkas, J.A, J.W. Picking and T.J. Santangelo. 2013.  Genetic techniques for the Archaea.  Annual Review of Genetics. 47:539-61. 

3- Santangelo, T.J. and I. Artsimovitch. 2011. Termination and antitermination: RNA polymerase runs a stop sign. Nat Rev Microbiol. 9:319-29.

2- Bai, L., Santangelo, T.J., Wang, M.D. 2006. Single-Molecule Analysis of RNA Polymerase Transcription. Annual Review of Biophysics and Biomolecular Structure. Feb 17.

1- Santangelo, T.J., and Roberts, J.W. 2002. RfaH, a bacterial transcription antiterminator. Mol Cell 9: 698-700.

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NIH PubMed Publications List