M. Mitchell Smith

Education

  • BA, Johns Hopkins University, Baltimore MD
  • Postdoc, Johns Hopkins University, Baltimore MD
  • Postdoc, Edinburgh University, Edinburgh, Scotland, UK
  • PhD, Johns Hopkins University, Baltimore MD

Primary Appointment

  • Professor, Microbiology, Immunology, and Cancer Biology

Contact

Research Interest(s)

Functional Genomics of Histones, Chromatin, and Protein Acetylation Signaling in Cancer and the Cell Cycle

Research Description

My laboratory is interested in the molecular genetics of eukaryotic chromosome structure and function, including the mechanisms of gene transcription, DNA replication, recombination, and chromosome segregation. Our research focuses on the genes that encode the histone proteins which comprise the protein subunits of the nucleosome, the primary building block of the eukaryotic chromosome. Thus, the histones are critical for chromosome structure and dynamics, and their function is required at key steps in the cell division cycle. Our experiments exploit the advanced molecular genetics of the simple eukaryote Saccharomyces cerevisiae, budding yeast. Yeast provides an experimental system that is advantageous for cell biology, biochemistry, and molecular genetic studies. A powerful collection of classical genetic and molecular techniques have been developed for yeast that permit the recombinant DNA cloning and manipulation of genes in vitro and the characterization of new mutants in vivo. Currently, we are focusing on four main research questions:

The roles of the histone amino-terminal tail domains in chromatin structure and function, particularly in DNA replication and the maintenance of genome integrity. The roles of the nucleosome in regulating gene transcription, and how histone-histone interactions function in shaping the chromatin template. The roles of the histones in determining the structure and morphogenesis of the centromere of the chromosome. The roles of the "SNF/SWI" complex in remodeling chromatin for transcription, and its interaction with the adenovirus E1A oncoprotein.

Selected Publications

  • Hang M, Smith M. Genetic analysis implicates the Set3/Hos2 histone deacetylase in the deposition and remodeling of nucleosomes containing H2A.Z. Genetics. 2011;187(4): 1053-66. PMID: 21288874 | PMCID: PMC3070515
  • Jensen K, Santisteban M, Urekar C, Smith M. Histone H2A.Z acid patch residues required for deposition and function. Molecular genetics and genomics : MGG. 2011;285(4): 287-96. PMID: 21359583 | PMCID: PMC3253533
  • Santisteban M, Hang M, Smith M. Histone variant H2A.Z and RNA polymerase II transcription elongation. Molecular and cellular biology. 2011;31(9): 1848-60. PMID: 21357739 | PMCID: PMC3133230
  • Baker S, Phillips J, Anderson S, Qiu Q, Shabanowitz J, Smith M, Yates J, Hunt D, Grant P. Histone H3 Thr 45 phosphorylation is a replication-associated post-translational modification in S. cerevisiae. Nature cell biology. 2010;12(3): 294-8. PMID: 20139971 | PMCID: PMC2856316
  • French S, Sikes M, Hontz R, Osheim Y, Lambert T, El Hage A, Smith M, Tollervey D, Smith J, Beyer A. Distinguishing the roles of Topoisomerases I and II in relief of transcription-induced torsional stress in yeast rRNA genes. Molecular and cellular biology. 2010;31(3): 482-94. PMID: 21098118 | PMCID: PMC3028620
  • Iizuka M, Takahashi Y, Mizzen C, Cook R, Fujita M, Allis C, Frierson H, Fukusato T, Smith M. Histone acetyltransferase Hbo1: catalytic activity, cellular abundance, and links to primary cancers. Gene. 2009;436(1): 108-14. PMID: 19393168 | PMCID: PMC2674512