Professor Max E. Gottesman Phone: 212-305-6900 Lab Phone: 212-305-3705 Fax: 212-305-1741 Email: meg8@columbia.edu

Professor Max E. Gottesman
Phone: 212-305-6900
Lab Phone: 212-305-3705
Fax: 212-305-1741
Email: meg8@columbia.edu

Max E. Gottesman, M.D., Ph.D.

Charles H. Revson Professor of Biochemistry & Molecular Biophysics and Microbiology & Immunology
Member, American Academy of Arts & Sciences
Fellow, American Association for the Advancement of Science
M.D., Ph.D., Yale University

Transcription termination in E. coli and bacteriophage, repair of double-strand breaks in eukaryotic DNA

Research
Our laboratory studies the regulation of transcription termination in E. coli and its bacteriophage. We are particularly interested in how transcription termination relates to translation and to DNA replication and chromosome integrity. We study how transcription and translation are coupled in E. coli, and the role of the NusG/Spt5 protein in linking RNAP to the lead ribosome. Another area of research concerns the mechanism of DNA double-strand break repair in Xenopus oocyte extracts and in mammalian cells.

The laboratory is no longer accepting students.

 

Selected Publications

  1. Zagelbaum, J., Schooley, A., Zhao, J., Schrank, B.R., Callen, E., Zha, S., Gottesman, M.E., Nussenzweig, A., Rabadan, R., Dekker, J. and Gautier, J. (2023) Multiscale reorganization of the genome following DNA damage facilitates chromosome translocations via nuclear actin polymerization. Nature Struct. Mol. Biol. 30: 99–106. https://doi.org/10.1038/s41594-022-00893-6

  2. Bailey, E.J., Gottesman, M.E. and Gonzalez, R.L., Jr (2022) NusG-mediated coupling of transcription and translation enhances gene expression by suppressing RNA polymerase backtracking. J. Mol. Biol. 434: 167330. https://doi.org/10.1016/j.jmb.2021.167330

  3. Gottesman, M.E. and Mustaev, A. (2019). Ribonucleoside-5'-diphosphates (NDPs) support RNA polymerase transcription, suggesting NDPs may have been substrates for primordial nucleic acid biosynthesis. J. Biol. Chem. 294: 11785–11792. https://doi.org/10.1074/jbc.RA119.009074

  4. Pezone, A., Zuchegna, C., Tramontano, A., Romano, A., Russo, G., de Rosa, M., Vinciguerra, M., Porcellini, A., Gottesman, M.E. and Avvedimento, E.V. (2019) RNA stabilizes transcription-dependent chromatin loops induced by nuclear hormones. Sci. Rep. 9: 3925. https://doi.org/10.1038/s41598-019-40123-6

  5. Schrank, B.R., Aparicio, T., Li, Y., Chang, W., Chait, B.T., Gundersen, G.G., Gottesman, M.E., & Gautier, J. (2018) Nuclear ARP2/3 drives DNA break clustering for homology-directed repair. Nature 559: 61–66. https://doi.org/10.1038/s41586-018-0237-5

  6. Saxena, S., Myka, K.K., Washburn, R., Costantino, N., Court, D.L. and Gottesman, M.E. (2018) Escherichia coli transcription factor NusG binds to 70S ribosomes. Mol. Microbiol. 108: 495–504. https://doi.org/10.1111/mmi.13953

  7. Gottesman, M.E. and Mustaev, A. (2018) Inorganic phosphate, arsenate, and vanadate enhance exonuclease transcript cleavage by RNA polymerase by 2000-fold. Proc. Natl. Acad. Sci. U.S.A. 115: 2746–2751. https://doi.org/10.1073/pnas.1720370115

  8. Kang, J.Y., Olinares, P.D., Chen, J., Campbell, E.A., Mustaev, A., Chait, B.T., Gottesman, M.E. and Darst, S.A. (2017) Structural basis of transcription arrest by coliphage HK022 nun in an Escherichia coli RNA polymerase elongation complex. Elife 6: e25478.

  9. Mustaev, A., Roberts, J. and Gottesman, M. (2017) Transcription elongation. Transcription 8:150-161.

  10. Kato, N., Kawasoe, Y., Williams, H., Coates, E., Roy, U., Shi, Y., Beese, L.S., Scharer, O.D., Yan, H., Gottesman, M.E., Takahashi, T.S. and Gautier, J. Sensing and processing of DNA interstrand crosslinks by the mismatch repair pathway. Cell Rep. 21: 1375-1385.

  11. Pezone, A., Russo, G., Tramontano, A., Florio, E., Scala, G., Landi, R., Zuchegna, C., Romano, A., Chiariotti, L., Muller, M.T., Gottesman, M.E., Porcellini, A. and Avvedimento, E.V. (2017) High-coverage methylation data of a gene model before and after DNA damage and homologous repair. Sci. Data 4: 170043.

  12. Kang, J.Y., Olinares, P.D., Chen, J., Campbell, E.A., Mustaev, A., Chait, B.T., Gottesman, M.E. and Darst, S.A. (2017) Structural basis of transcription arrest by coliphage HK022 Nun in an Escherichia coli RNA polymerase elongation complex. Elife pii: e25478.

  13. Russo, G., Landi, R., Pezone, A., Morano, A., Zuchegna, C., Romano, A., Muller, M.T., Gottesman, M.E., Porcellini, A. and Avvedimento, E.V. (2016) DNA damage and repair modify DNA methylation and chromatin domain of the targeted locus: Mechanism of allele methylation polymorphism. Sci. Rep. 6: 33222.

  14. Mustaev, A., Vitiello, C.L. and Gottesman, M.E. (2016) Probing the structure of Nun transcription arrest factor bound to RNA polymerase. Proc. Natl. Acad. Sci. U.S.A. 113: 8693-8698.

  15. Washburn, R.S. and Gottesman, M.E. (2015) Regulation of transcription elongation and termination. Biomolecules 5: 1063-1078.

  16. Vitiello, C.L. and Gottesman, M.E. (2014) Bacteriophage HK022 Nun protein arrests transcription by blocking lateral mobility of RNA polymerase during transcription elongation. Bacteriophage 4: e32187.

  17. Lignitto, L., Arcella, A., Sepe, M., Rinaldi, L., Delle Donne, R., Gallo, A., Stefan, E., Bachmann, V.A., Oliva, M.A., Tiziana Storlazzi, C., L'Abbate, A., Brunetti, A., Gargiulo, S., Gramanzini, M., Insabato, L., Garbi, C., Gottesman, M.E. and Feliciello, A. (2013) Proteolysis of MOB1 by the ubiquitin ligase praja2 attenuates Hippo signalling and supports glioblastoma growth. Nature Commun. 4: 1822.

  18. Peterson, S.E., Li, Y., Wu-Baer, F., Chait, B.T., Baer, R., Yan, H., Gottesman, M.E. and Gautier, J. (2013) Activation of DSB processing requires phosphorylation of CtIP by ATR. Mol. Cell 49: 657-667.

  19. Bubunenko, M., Court, D.L., Al Refaii, A., Saxena, S., Korepanov, A., Friedman, D.I., Gottesman, M.E. and Alix, J.H. (2013) Nus transcription elongation factors and RNase III modulate small ribosome subunit biogenesis in Escherichia coli. Mol. Microbiol. 87: 382-393.

  20. Williams, H.L., Gottesman, M.E. and Gautier, J. (2012) Replication-independent repair of DNA interstrand crosslinks. Mol. Cell. 47: 140-147.

  21. Dutta, D., Shatalin, K., Epshtein, V., Gottesman, M.E. and Nudler, E. (2011) Linking RNA polymerase backtracking to genome instability in E. coli. Cell 146: 533-543.

  22. Washburn, R.S. and Gottesman, M.E. (2011) Transcription termination maintains chromosome integrity. Proc. Natl. Acad. Sci. U.S.A. 108: 792-797.

  23. Burmann, B.M., Schweimer, K., Luo, X., Wahl, M.C., Stitt, B.L., Gottesman, M.E. and Rosch, P. (2010) A NusG:NusE complex links transcription and translation. Science 328: 501-504.

  24. Ben-Yehoyada, M., Wang L.C., Kozekov, I.D., Rizzo, C.J., Gottesman, M.E. and Gautier, J. (2009) Checkpoint signaling from a single DNA interstrand crosslink. Mol. Cell. 35: 704-15.

  25. Mooney, R.A., Schweimer, K., Roesch, P., Gottesman, M. and Landick, R. (2009) Two structurally independent domains of E. coli NusG create regulatory plasticity via distinct interactions with RNA polymerase and regulators. J. Mol. Biol. 391: 341-58.

  26. Luo, X., Hsiao, H-H., Bubunenko, M., Weber, G., Court, D.L., Gottesman, M.E., Urlaub, H. and Wahl, M.C. (2008) Structural and functional analysis of the E. coli NusB-S10 transcription antitermination complex. Mol. Cell 32: 791-802.

  27. Kim, H.C. and Gottesman, M.E. (2004) Transcription termination by phage HK022 Nun is facilitated by COOH-terminal lysine residues. J. Biol. Chem 279: 13412-13417.

  28. Feliciello, A., Gottesman, M.E., and Avvedimento, E.V. (2005) cAMP-PKA signaling to the mitochondria: protein scaffolds, mRNA and phosphatases. Cellular Signalling 17: 279-287

  29. Kim, H.C., Washburn, R.S, and Gottesman M.E. (2006) Role of E. coli NusA in Phage HK022 Nun-mediated Transcription Termination. J. Mol. Biol. 359: 10-12