|MAX E. GOTTESMAN
Phone: 212- 305-6900
We study transcription termination in E. coli. Structures of the E. coli NusA, NusB, NusE and NusG protein, which are required for termination, have been determined. We are performing structure-function analyses of these functions both in vivo and in purified in vitro systems. We have shown that NusG forms a linkage between elongating RNA polymerase and the first ribosome. Our work also bears on the relationship between transcription termination and chromosome integrity.
We also study how phage HK022 Nun protein inhibits phage lambda gene expression by. Nun, which is homologous to the HIV TAT protein, binds to specific sequences in lambda nascent mRNA and blocks translocation of RNA polymerase. Nun also contacts lambda DNA template both upstream and downstream to the stalled RNA polymerase. We are interested in the detailed biochemistry of this reaction and its role in the life cycle of HK022.
In collaboration with Dr. J. Gautier, we analyze DNA damage repair in eukaryotic systems with emphasis on double-strand breaks (DSB) and interstrand crosslinks (ICL). A cell free Xenopus egg extract that repairs ICL has been established. We are determining the components of this repair pathway and the DNA intermediates that are generated.
In collaboration with Dr. E. Avvedimento, we find that DSB repair in mammalian cells is associated with DNA methylation and gene silencing. The components of this reaction are being defined.
cAMP signals are transduced to different parts of the eukaryotic cell. The subcellular location of PKA is of critical importance in transmission of these signals. PKA is localized to different subcellular compartments by a family of anchoring proteins, the AKAPs. The relationship between PKA anchoring and cAMP signal transduction is being studied in cultured cell lines.
Recent and Notable Articles
Cardinale CJ, Washburn RS, Tadigotla VR, Lewis M. Brown LM, Gottesman ME, and Nudler E. Termination Factor Rho and Its Cofactors NusA and NusG Silence Foreign DNA in E. coli. Science, 320:935-8. (2008).
Björn M. Burmann B, Schweimer K, Luo X, Wahl MC, Stitt BL, Gottesman ME, and Rösch P. A NusG:NusE complex links transcription and translation. Science, 328:501-4. (2010).
Ben-Yehoyada M, Wang LC, Kozekov ID, Rizzo CJ, Gottesman ME and Gautier J. Checkpoint signaling from a single DNA interstrand crosslink. Mol Cell. 35:704-15. (2009).
Cuozzo C, Porcellini A, Angrisano T, Morano A, Lee B, Pardo AD, Messina S, Iuliano R, Fusco A, Santillo MR, Muller MT, Chiariotti L, Gottesman ME, and Avvedimento EV.DNA Damage, Homology-Directed Repair, and DNA Methylation. PLoS Genet. 3:e110 (2007). Comment in Nature Reviews Genetics 8:492 (2007).
Carlucci A, Porpora M, Garbi C, Galgani M, Santoriello M, Mascolo M, di Lorenzo D, Altieri V, Quarto M, Terracciano L, Gottesman ME, Insabato L, Feliciello A. PTPD1 supports receptor stability and mitogenic signaling in bladder cancer cells. J Biol Chem. Oct 5 (2010 ).