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Reines Laboratory

Daniel Reines, Ph.D.


Daniel ReinesCurrent research is focusing on two different aspects of the biochemistry and molecular biology of gene expression. Project 1 is a study of transcription elongation by RNA polymerase II. Gene expression can be controlled by governing the ability of RNA polymerase to transcribe a full-length RNA transcript. We have characterized the structure of normal and arrested elongation complexes. Arrested complexes attain an unusual structure and can be isomerized into an active form through the function of elongation factor SII and a special enzymatic activity of RNA polymerase II; a nascent transcript ribonuclease. Our focus now has been toward the in vivo role of this factor. We are employing S. cerevisiae to study elongationally compromised RNA polymerase enzymes in vitro and transcription in vivo in cells mutant for elongation machinery components. We are focusing on the enzyme IMP dehydrogenase whose activity is co-regulated with cell growth rates. Sequences in the promoter of one of the 4 yeast IMPDH genes is responsible for sensing guanine nucleotide levels in cells and inducing transcription of the gene. We are currently dissecting this regulatory mechanism. Project 2 is a collaborative investigation into the fragile X syndrome which is the most common form of inherited mental retardation. The disease results from a CGG triplet repeat expansion mutation in the 5’ untranslated region of FMR1 which results in the subsequent methylation and silencing of the gene. We are studying the mechanism by which FMR1 gene is transcribed in healthy individuals, as well as why it is inactive in patients with the syndrome. We have identified a change in the chromatin structure of FMR1 concomitant with the mutation and methylation of the DNA. Histones modifications show the gene to be ‘heterochromatinized’ in patient cells. We are currently examining the transcription factors that run this promoter normally and how they are inactive in patient cells. Finally, we are testing designer DNA binding proteins that can be used in patient cells to reverse the effects of the heterochromatinization and silencing of FMR1.

Current Members of the Reines Lab

Travis Loya
Grad Student
Thomas O'Rourke
Research Specialist, Lead

Contact Information

Department of Biochemistry
1510 Clifton Rd. NE
Atlanta, GA 30322

O. Wayne Rollins Center
4023 Office
4008 Lab
404.727.3361 (Office tel.)
404.727.3693 (Lab tel.)
404.727.2738 (Fax)