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

Proc Natl Acad Sci U S A. 2000 Jul 5;97(14):7927-32. doi: 10.1073/pnas.97.14.7927.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Chromosome Mapping
  • Chromosomes, Human, Pair 3
  • DNA Repair*
  • DNA Replication*
  • DNA-Binding Proteins / metabolism*
  • Expressed Sequence Tags
  • Gene Library
  • Humans
  • Ligases / metabolism
  • Methyl Methanesulfonate / pharmacology
  • Mitomycin / pharmacology
  • Molecular Sequence Data
  • Mutagens / pharmacology*
  • Polymerase Chain Reaction
  • Protein Binding
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Two-Hybrid System Techniques
  • Ubiquitin-Conjugating Enzymes
  • Ultraviolet Rays / adverse effects

Substances

  • DNA-Binding Proteins
  • Mutagens
  • RAD18 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Mitomycin
  • Methyl Methanesulfonate
  • Ubiquitin-Conjugating Enzymes
  • Ligases

Associated data

  • GENBANK/AB035274