MAX E. GOTTESMAN

MAX E. GOTTESMAN Email: gottesma@cancercenter.columbia.edu Phone: 212- 305-6900 Location: HHSC-914

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. In a related project, we study the inhibition of phage l gene expression by phage HK022 Nun protein. Nun, which is homologous to the HIV TAT protein, binds to specific sequences in l nascent mRNA and blocks translocation of RNA polymerase. Nun also contacts l DNA template just promoter-distal to the stalled RNA polymerase. We are interested in the detailed biochemistry of this reaction and its role in the life cycle of HK022.

We also study DNA damage repair in eukaryotic systems with emphasis on double-strand breaks (DSB) and interstrand crosslinks (ICL). We find that DSB repair in mammalian cells is associated with DNA methylation and gene silencing. The recruitment of DNA methylase and its mode of action are under investigation. 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.

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 tranduction is being studied in cultured cell lines.

Recent and Notable Articles

Costanzo, V., Shechter, D., Lupardus, P.J., Cimprich, K.A., Gottesman, M. and Gautier, J. An ATR- and Cdc7-dependent DNA damage checkpoint that inhibits initiation of DNA replication. Mol. Cell. 11:203-213 (2003).

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, Adornetto A, Scorziello A, Foca M, Viggiano D, Annunziato L, Gottesman M and Feliciello A. Regulated proteolysis of AKAP121 controls  mitochondrial response to hypoxia. EMBO J. 27:1073-84 (2008).

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).

Uc-Mass A, Khodursky A, Brown L, Gottesman ME. Overexpression of phage HK022 Nun protein is toxic for Escherichia coli. J Mol Biol. 380:812-9. (2008).