RAD18

E3 ubiquitin-protein ligase RAD18 is an enzyme that in humans is encoded by the RAD18 gene. A knockout in a human colorectal cancer cell line, HCT116, has also been created.

Function

The protein encoded by this gene is highly similar to S. cerevisiae DNA damage repair protein Rad18. Yeast Rad18 functions through 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.

RAD18 is an E3 ubiquitin ligase that enables movement of ubiquitin from a ubiquitin carrier to another protein (the substrate). One activity of RAD18 is to prevent replication fork collapse by promoting DNA translesion synthesis and template switching. RAD18 is also involved in directing repair of DNA double-strand breaks by homologous recombination in post replicative chromatin. RAD18 appears to promote homologous recombinational repair by recruiting the SMC5,SMC6 (SMC5/6) complex to the DNA breaks.

Interactions

RAD18 has been shown to interact with HLTF, UBE2B and UBE2A.