DNA polymerase iota and related Rad30-like enzymes

Until recently, the molecular mechanisms of translesion DNA synthesis (TLS) , a process whereby a damaged base is used as a template for continued repl ication, was poorly understood. This area of scientific research has, howev er, been revolutionized by the finding that proteins long implicated in TLS are, in fact, DNA polymerases. Members of this so-called UmuC/DinB/Rev1/Ra d30 superfamily of polymerases have been identified in prokaryotes, eukaryo tes and archaea. Biochemical studies with the highly purified polymerases r eveal that some, but not all, can traverse blocking lesions in template DNA . All of them share a common feature, however, in that they exhibit low fid elity when replicating undamaged DNA. Of particular interest to us is the R ad30 subfamily of polymerases found exclusively in eukaryotes. Humans posse ss two Rad30 paralogs, Rad30A and Rad30B. The RAD30A gene encodes DNA polym erase eta and defects in the protein lead to the xeroderma pigmentosum vari ant (XP-V) phenotype in humans. Very recently RAD30B has also been shown to encode a novel DNA polymerase, designated as Pol iota. Based upon in vitro studies, it appears that Pol iota has the lowest fidelity of any eukaryoti c polymerase studied to date and we speculate as to the possible cellular f unctions of such a remarkably error-prone DNA polymerase.