Dysfunction of human Rad18 results in defective postreplication repair andhypersensitivity to multiple mutagens

Postreplication repair functions in gap-filling of a daughter strand on rep lication of damaged DNA, The yeast Saccharomyces cerevisiae Rad18 protein p lays a pivotal role in the process together with the Rad6 protein. Here, we have cloned a human homologue of RAD18, hRAD18, It maps on chromosome 3p24 -25, where deletions are often found in lung, breast, ovary, and testis can cers. In vivo, hRad18 protein binds to hHR6 protein through a conserved rin g-finger motif, Stable transformants with hRad18 mutated in this motif beco me sensitive to UV, methyl methanesulfonate, and mitomycin C, and are defec tive in the replication of UV-damaged DNA, Thus, hRAD18 is a functional hom ologue of RAD18.