The human RAD18 gene product interacts with HHR6A and HHR6B

During DNA replication, lesion bypass is an important cellular response to unrepaired damage in the genome. In the yeast Saccharomyces cerevisiae, Rad 6 and Rad18 are required for both the error-free and error-prone lesion byp ass mechanisms, Furthermore, Rad6-Rad18 interaction is thought to be critic al at an early step during lesion bypass in yeast. Two closely related huma n homologs of yeast Rad6 have been identified as HHR6A and HHR6B, Here, we report a full-length cDNA coding for the human homolog of yeast Rad18, The human RAD18 gene codes for a protein of 484 amino acid residues with a calc ulated molecular weight of 54 804 Da, and the gene is localized to chromoso me 3 between reference intervals D3S3591 and D3S1283, Human RAD18 protein ( hRAD18) was found to interact with HHR6A and HHR6B. When co-expressed in ye ast cells, stable hRAD18-HHR6A and hRAD18-HHR6B protein complexes were iden tified and purified to near homogeneity, Thus, through interaction and comp lex formation with HHR6A and HHR6B, RAD18 protein may play an important rol e in lesion bypass mechanisms in humans. Consistent with its role as a fund amental lesion bypass protein, the RAD18 gene is ubiquitously expressed in various human tissues.