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 replication, was poorly understood. This area of scientific research has, however, been revolutionized by the finding that proteins long implicated in TLS are, in fact, DNA polymerases. Members of this so-called UmuC/DinB/Rev1/Rad30 superfamily of polymerases have been identified in prokaryotes, eukaryotes and archaea. Biochemical studies with the highly purified polymerases reveal 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 fidelity when replicating undamaged DNA. Of particular interest to us is the Rad30 subfamily of polymerases found exclusively in eukaryotes. Humans possess two Rad30 paralogs, Rad30A and Rad30B. The RAD30A gene encodes DNA polymerase eta and defects in the protein lead to the xeroderma pigmentosum variant (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 eukaryotic polymerase studied to date and we speculate as to the possible cellular functions of such a remarkably error-prone DNA polymerase.
McDonald
J P
JP
Section on DNA Replication, Repair and Mutagenesis, National Institute of Child Health and Human Development, Bethesda, MD 20892-2725, USA.
Tissier
A
A
Frank
E G
EG
Iwai
S
S
Hanaoka
F
F
Woodgate
R
R
D001426:Bacterial Proteins / Q000502:physiology; D004259:DNA-Directed DNA Polymerase / Q000502:physiology*; D029968:Escherichia coli Proteins; D006801:Humans; D011506:Proteins / Q000502:physiology*; D012441:Saccharomyces cerevisiae / Q000502:physiology; D000094769:DNA Polymerase iota; D000099270:Y-Family DNA Polymerases
D001426:Bacterial Proteins; D004259:DNA-Directed DNA Polymerase; D029968:Escherichia coli Proteins; D011506:Proteins; D000094769:DNA Polymerase iota; C094399:DinB protein, E coli; C078202:UmuC protein, E coli; C404302:POLK protein, human; D000099270:Y-Family DNA Polymerases; C112338:Rad30 protein