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

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.

SUBMITTER: Tateishi S

PROVIDER: S-EPMC16647 | biostudies-literature | 2000 Jul

REPOSITORIES: biostudies-literature

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

Tateishi S S Sakuraba Y Y Masuyama S S Inoue H H Yamaizumi M M

Proceedings of the National Academy of Sciences of the United States of America 20000701 14

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 m ...[more]

PMID: 10884424

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