My research interests concern structure-function relationships in the eukaryotic chromosome. Conformational changes in chromosomal DNA have been implicated in the regulation of DNA replication and transcription. The research program in my laboratory involve identification and functional characterization of non-histone proteins that bind DNA and affect DNA/chromatin conformations. Our work focused on a DNA helix-destabilizing protein (HDP) which we purified from various cell types. This protein binds preferentially to single-stranded DNA and lowers the melting temperature of double-stranded DNA. Using immunological techniques we found that it is present in such diverse organisms as man, rodent and dipteran, and it is concentrated on dipteran polytene chromosomes at developmental and heat-shock induced sites active in transcription. Microinjection of antibodies generated against the HDP into salivary gland cells of insect larvae caused dramatic inhibition of transcription. Structural analyses of this HDP led us to a surprising discovery of its homology to the isozyme lactate dehydrogenase-5 (LDH-5). Biological significance of this apparent homology is presently unclear.
Molecular biology; role of nonhistone proteins in the structure and regulation of chromatin
Williams, K.R., S. Reddigari, and G.L. Patel. 1985. "Identification of a nucleic acid helix-destablizing protein from rat liver as lactate dehydrogenase-5." Proc. Natl. Aca. Sci. USA 85:5260-5264.
Fechheimer, M., J.F. Boylan, S. Parker, J.E. Sisken, G.L. Patel, and S.G. Zimmer. 1987. "Transfection of mammalian cells with plasmid DNA by scrape loading and sonication loading." Proc. Natl. Acad. Sci. 84:8463-8467.
Egyhazi, E., M. Holst, A. Pigon, J. Stigare, and G.L. Patel. 1989. "Effects of a DNA helix-destabilizing protein on transcription in living cells." Eur. J. Cell Biol. 48:88-94.