Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens.
Postreplication repair functions in gap-filling of a daughter strand on replication of damaged DNA. The yeast Saccharomyces cerevisiae Rad18 protein plays 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 cancers. In vivo, hRad18 protein binds to hHR6 protein through a conserved ring-finger motif. Stable transformants with hRad18 mutated in this motif become sensitive to UV, methyl methanesulfonate, and mitomycin C, and are defective in the replication of UV-damaged DNA. Thus, hRAD18 is a functional homologue of RAD18.
Tateishi
S
S
Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862-0976, Japan.
Sakuraba
Y
Y
Masuyama
S
S
Inoue
H
H
Yamaizumi
M
M
D000595:Amino Acid Sequence; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020224:Expressed Sequence Tags; D015723:Gene Library; D006801:Humans; D008025:Ligases / Q000378:metabolism; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D016685:Mitomycin / Q000494:pharmacology; D008969:Molecular Sequence Data; D009153:Mutagens / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D020798:Two-Hybrid System Techniques; D044763:Ubiquitin-Conjugating Enzymes; D014466:Ultraviolet Rays / Q000009:adverse effects
D004268:DNA-Binding Proteins; D009153:Mutagens; C063607:RAD18 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D016685:Mitomycin; D008741:Methyl Methanesulfonate; D044763:Ubiquitin-Conjugating Enzymes; D008025:Ligases