A full-length cDNA of hREV3 is predicted to encode DNA polymerase ζ for damage-induced mutagenesis in humans

DNA damage can cause mutations which in turn may lead to carcinogenesis. In the yeast Saccharomyces cerevisiae, DNA damage-induced mutagenesis pathway requires the REV3 gene. It encodes the catalytic subunit of DNA polymerase ζ that specifically functions in translesion DNA synthesis. We have cloned a cDNA of the human homologue of REV3 (hREV3), which consists of 10,716 bp and codes for a protein of 3130 amino acid residues (352,737 Da). Its C-terminal 755 amino acids show extensive homology with the yeast protein at the C-terminus: 43% identity and 74% similarity. This region contains the six highly conserved DNA polymerase motifs. Furthermore, we have identified four sequence motifs in the N-terminal region outside the polymerase domain that are conserved in DNA polymerase δ from various sources. Three of which are present in DNA polymerase ζ encoded by human, yeast, and plant REV3 genes, indicating that this protein is a member of the DNA polymerase δ family. DNA polymerases δ and ζ are structurally distinguished by the presence of a specific δIV motif in the former and motifs ζI and ζII in the latter, respectively. Human DNA polymerase ζ is ubiquitously expressed in various tissues, consistent with the notion that the hREV3 pathway may be a fundamental mechanism of damage-induced mutagenesis in humans. Copyright (C) 1999 Elsevier Science B.V.