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Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7927-32.

Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens.

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  • 1Institute of Molecular Embryology and Genetics, Kumamoto University School of Medicine, Kumamoto 862-0976, Japan.

Abstract

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.

PMID:
10884424
[PubMed - indexed for MEDLINE]
PMCID:
PMC16647
Free PMC Article
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