The human heterodimeric Dr1/DRAP1 is a general transcription repressor extensively studied in vitro. The two proteins repress transcription by binding TATA-binding protein (TBP), inhibiting the formation of transcription preinitiation complex. Recently the counterparts of the human Dr1 and DRAP1 were identified and named YDR1 and BUR6, respectively, in the yeast Saccharomyces cerevisiae. The YDR1 gene is essential for cell viability. BUR6 is also essential for cell viability. The human Dr1 gene can replace the YDR1 gene in vivo. YDR1 overexpression in vivo confers slow growth phenotype. The YDR1 and BUR6 can be copurified in a gel filtration column, using affinity-purified polyclonal antibody against both yDr1 and Bur6 polypeptides. The gel mobility shift assay showed that Ydr1 and Bur6 repress in vitro transcription and this repression of basal transcription can be overcome by TBP, a global regulator. These results indicate that YDR1/BUR6 functions as a global repressor of transcription in vivo and directly targets TBP. We are currently mutagenizing YDR1 and BUR6 to study sturcuture-function of the two genes.