STRUCTURAL AND FUNCTIONAL CONSERVATION OF 2 HUMAN HOMOLOGS OF THE YEAST DNA-REPAIR GENE RAD6

The RAD6 gene of Saccharomyces cerevisiae encodes a ubiquitin-conjugating enzyme (E2) that is required for DNA repair, damage-induced mutagenesis, and sporulation. We have cloned the two human RAD6 homologs, designated HHR6A and HHR6B. The two 152-amino acid human proteins share 95% sequence identity with each other and almost-equal-to 70% and almost-equal-to 85% overall identity with the homologs from yeasts (S. cerevisiae and Schizosaccharomyces pombe) and Drosophila melanogaster, respectively. Neither of the human RAD6 homologs possesses the acidic C-terminal sequence present in the S. cerevisiae RAD6 protein. Genetic complementation experiments reveal that HHR6A as well as HHR6B can carry out the DNA repair and mutagenesis functions of RAD6 in S. cerevisiae rad6-DELTA mutants.