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

Mutat Res. 1999 Mar 10;433(2):89-98. doi: 10.1016/s0921-8777(98)00065-2.


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 zeta 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 delta from various sources. Three of which are present in DNA polymerase zeta encoded by human, yeast, and plant REV3 genes, indicating that this protein is a member of the DNA polymerase delta family. DNA polymerases delta and zeta are structurally distinguished by the presence of a specific delta IV motif in the former and motifs zeta I and zeta II in the latter, respectively. Human DNA polymerase zeta 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Catalytic Domain
  • Cloning, Molecular
  • DNA, Complementary
  • DNA-Binding Proteins
  • DNA-Directed DNA Polymerase / chemistry
  • DNA-Directed DNA Polymerase / genetics*
  • DNA-Directed DNA Polymerase / metabolism
  • Humans
  • Molecular Sequence Data
  • Mutagenesis
  • Sequence Homology, Amino Acid


  • DNA, Complementary
  • DNA-Binding Proteins
  • DNA-Directed DNA Polymerase
  • REV3L protein, human

Associated data

  • GENBANK/AF071798