RAD18

E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene.^[1][2][3]

The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through its interaction with Rad6, which is a ubiquitin-conjugating enzyme required for post-replication repair of damaged DNA. Similar to its yeast counterpart, this protein is able to interact with the human homolog of yeast Rad6 protein through a conserved ring finger motif. Mutation of this motif results in defective replication of UV-damaged DNA and hypersensitivity to multiple mutagens.^[3]

Animal models

Model organisms have been used in the study of RAD18 function. A conditional knockout mouse line, called Rad18^{tm1a(EUCOMM)Wtsi},^[4] was generated as part of the EUCOMM program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists — at the Wellcome Trust Sanger Institute.^{[5][6][7][8][9]} Mice lacking Rad18 had no significant defects in viability or fertility,^[10][11] therefore male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[6][12][13]

Twenty five tests were carried out and four significant phenotypes were reported:^[13]

• Mutant male mice had a decreased body weight compared to wildtype control mice.
• Mutant male mice showed increased activity, VO2 and energy expenditure, determined by indirect calorimetry.
• Dual-energy X-ray absorptiometry (DEXA) showed mutant male mice had a decrease in fat mass.
• A micronucleus test found a potential increase in DNA damage in mutant mice.

Interactions

RAD18 has been shown to interact with HLTF,^[20] UBE2B^[1][2] and UBE2A.^[1][2]

References

Further reading