Loss of function of S-II makes yeast sensitive to 6-azauracil. Here, we identified a multi-copy suppressor gene of this phenotype, termed SSM1 (suppressor of 6-azauracil sensitivity of the S-II null mutant 1), that encodes a novel protein consisting of 280 amino acid residues. Although both the SSM1 null mutant and the S-II/SSM1 double null mutant were viable under normal growth conditions, they resembled the S-II null mutant in being sensitive to 6-azauracil. Expression of the SSM1 gene was found to be repressed in the S-II null mutant but was restored by overexpression of chimeric S-II molecules that were able to stimulate transcription elongation by RNA polymerase II in vitro. Furthermore, we identified two transcription arrest sites within the transcription unit of the SSM1 gene in vitro that could be relieved by S-II. These results indicate that S-II confers yeast resistance to 6-azauracil by stimulating transcription elongation of the SSM1 gene.