The goals of this project are to determine the structure and function of the nuclear lamins. The lamins are Type V intermediate filament proteins that are found in the nuclear lamina and in the nucleoplasm. Mutations in the nuclear lamins have been linked to many human diseases including different forms of muscular dystrophy, cardiomyopathies and premature aging.
The specific aims of this grant are targeted towards a greater understanding of the function of the lamins in DNA replication, transcription, nuclear assembly and disassembly, and in the overall molecular architecture of the nucleus. Structural studies will be undertaken at both the light and electron microscope levels of resolution. Live cell imaging will also be used employing the jellyfish green fluorescent protein (GFP). Other methods will include the silencing of specific lamins using siRNA and a variety of biochemical and molecular methods aimed at determining the protein-protein interactions required for lamin assembly and structure. In addition, attempts will be made to identify the specific binding partners, which link the A and B-type lamins to the RNA polymerase II machinery and to the DNA replication elongation complex.
| Takeshi, Shimi; Pack, Chan-Gi; Goldman, Robert D (2016) Analyses of the Dynamic Properties of Nuclear Lamins by Fluorescence Recovery After Photobleaching (FRAP) and Fluorescence Correlation Spectroscopy (FCS). Methods Mol Biol 1411:99-111 |
| Butin-Israeli, Veronika; Adam, Stephen A; Jain, Nikhil et al. (2015) Role of lamin b1 in chromatin instability. Mol Cell Biol 35:884-98 |
| Shimi, Takeshi; Goldman, Robert D (2014) Nuclear lamins and oxidative stress in cell proliferation and longevity. Adv Exp Med Biol 773:415-30 |
| Guo, Yuxuan; Kim, Youngjo; Shimi, Takeshi et al. (2014) Concentration-dependent lamin assembly and its roles in the localization of other nuclear proteins. Mol Biol Cell 25:1287-97 |
| Funkhouser, Chloe M; Sknepnek, Rastko; Shimi, Takeshi et al. (2013) Mechanical model of blebbing in nuclear lamin meshworks. Proc Natl Acad Sci U S A 110:3248-53 |
| Adam, Stephen A; Butin-Israeli, Veronika; Cleland, Megan M et al. (2013) Disruption of lamin B1 and lamin B2 processing and localization by farnesyltransferase inhibitors. Nucleus 4:142-50 |
| Butin-Israeli, Veronika; Adam, Stephen A; Goldman, Robert D (2013) Regulation of nucleotide excision repair by nuclear lamin b1. PLoS One 8:e69169 |
| Shimi, Takeshi; Butin-Israeli, Veronika; Goldman, Robert D (2012) The functions of the nuclear envelope in mediating the molecular crosstalk between the nucleus and the cytoplasm. Curr Opin Cell Biol 24:71-8 |
| Butin-Israeli, Veronika; Adam, Stephen A; Goldman, Anne E et al. (2012) Nuclear lamin functions and disease. Trends Genet 28:464-71 |
| Adam, Stephen A; Goldman, Robert D (2012) Insights into the differences between the A- and B-type nuclear lamins. Adv Biol Regul 52:108-13 |
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